Olfaction - NSc 8217 Fall 2009


Representation of olfactory information in the primate orbitofrontal cortex

E. T. Rolls and H. D. Critchley and A. Treves

J Neurophysiol  75  1982-96  (1996)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=8734597

1. To analyze the information represented about individual odor stimuli in the responses of single olfactory neurons in the primate orbitofrontal area, neuronal responses were measured to a set of seven to nine odorants in macaques performing an olfactory discrimination task. The population of neurons analyzed had responses that were significantly differential to the odorants. 2. Information theoretic analyses were applied to the responses of the neurons, and information measures were calculated from the firing rate of the responses and from the principal components of the responses. The information reflected by the firing rate of the response accounted for the majority of the information present (86\%) when compared with the information derived from the first three principal components of the spike train. This indicated that temporal encoding had a very minor role in the encoding of olfactory information by single orbitofrontal olfactory cells. 3. The average information about which odorant was presented, averaged across the 38 neurons, was 0.09 bits, a figure that is low when compared with the information values previously published for the responses of temporal lobe face-selective neurons. 4. Application of information theoretic analyses to the responses of these neurons showed how much information about which stimulus was delivered was present in the responses of individual neurons. It was found that for the majority of the neurons significant amounts of information were reflected about one or two of the odorants presented. 5. For each neuron, the information reflected in the responses of that neuron about the reinforcement value and the information about the identity of the odorants were calculated. It is shown that many neurons carry information about which of the odorants was presented; in addition, some neurons reflect information only about the taste association of the stimuli and not about odorant identity. 6. Measurements of the sparseness of the representation indicated that a broadly distributed representation of the identity of odorants was present in this population of neurons.



Encoding of Olfactory Information with Oscillating Neural Assemblies

G. Laurent and H. Davidowitz

Science  265  1872-1875  (1994)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17797226

In the brain, fast oscillations of local field potentials, which are thought to arise from the coherent and rhythmic activity of large numbers of neurons, were observed first in the olfactory system and have since been described in many neocortical areas. The importance of these oscillations in information coding, however, is controversial. Here, local field potential and intracellular recordings were obtained from the antennal lobe and mushroom body of the locust Schistocerca americana. Different odors evoked coherent oscillations in different, but usually overlapping, ensembles of neurons. The phase of firing of individual neurons relative to the population was not dependent on the odor. The components of a coherently oscillating ensemble of neurons changed over the duration of a single exposure to an odor. It is thus proposed that odors are encoded by specific but dynamic assemblies of coherently oscillating neurons. Such distributed and temporal representation of complex sensory signals may facilitate combinatorial coding and associative learning in these, and possibly other, sensory networks.



Impaired odour discrimination on desynchronization of odour-encoding neural assemblies

M. Stopfer and S. Bhagavan and B. H. Smith and G. Laurent

Nature  390  70-4  (1997)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=9363891

Stimulus-evoked oscillatory synchronization of neural assemblies has been described in the olfactory and visual systems of several vertebrates and invertebrates. In locusts, information about odour identity is contained in the timing of action potentials in an oscillatory population response, suggesting that oscillations may reflect a common reference for messages encoded in time. Although the stimulus-evoked oscillatory phenomenon is reliable, its roles in sensation, perception, memory formation and pattern recognition remain to be demonstrated--a task requiring a behavioural paradigm. Using honeybees, we now demonstrate that odour encoding involves, as it does in locusts, the oscillatory synchronization of assemblies of projection neurons and that this synchronization is also selectively abolished by picrotoxin, an antagonist of the GABA(A) (gamma-aminobutyric acid) receptor. By using a behavioural learning paradigm, we show that picrotoxin-induced desynchronization impairs the discrimination of molecularly similar odorants, but not that of dissimilar odorants. It appears, therefore, that oscillatory synchronization of neuronal assemblies is functionally relevant, and essential for fine sensory discrimination. This suggests that oscillatory synchronization and the kind of temporal encoding it affords provide an additional dimension by which the brain could segment spatially overlapping stimulus representations.


Who reads temporal information contained across synchronized and oscillatory spike trains?

K. MacLeod and A. Bäcker and G. Laurent

Nature  395  693-8  (1998)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=9790189

Our inferences about brain mechanisms underlying perception rely on whether it is possible for the brain to 'reconstruct' a stimulus from the information contained in the spike trains from many neurons. How the brain actually accomplishes this reconstruction remains largely unknown. Oscillatory and synchronized activities in the brain of mammals have been correlated with distinct behavioural states or the execution of complex cognitive tasks and are proposed to participate in the 'binding' of individual features into more complex percepts. But if synchronization is indeed relevant, what senses it? In insects, oscillatory synchronized activity in the early olfactory system seems to be necessary for fine odour discrimination and enables the encoding of information about a stimulus in spike times relative to the oscillatory 'clock. Here we study the decoding of these coherent oscillatory signals. We identify a population of neurons downstream from the odour-activated, synchronized neuronal assemblies. These downstream neurons show odour responses whose specificity is degraded when their inputs are desynchronized. This degradation of selectivity consists of the appearance of responses to new odours and a loss of discrimination of spike trains evoked by different odours. Such loss of information is never observed in the upstream neurons whose activity is desynchronized. These results indicate that information encoded in time across ensembles of neurons converges onto single neurons downstream in the pathway.



Encoding predicted outcome and acquired value in orbitofrontal cortex during cue sampling depends upon input from basolateral amygdala

G. Schoenbaum and B. Setlow and M. P. Saddoris and M. Gallagher

Neuron  39  855-67  (2003)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=12948451

Certain goal-directed behaviors depend critically upon interactions between orbitofrontal cortex (OFC) and basolateral amygdala (ABL). Here we describe direct neurophysiological evidence of this cooperative function. We recorded from OFC in intact and ABL-lesioned rats learning odor discrimination problems. As rats learned these problems, we found that lesioned rats exhibited marked changes in the information represented in OFC during odor cue sampling. Lesioned rats had fewer cue-selective neurons in OFC after learning; the cue-selective population in lesioned rats did not include neurons that were also responsive in anticipation of the predicted outcome; and the cue-activated representations that remained in lesioned rats were less associative and more often bound to cue identity. The results provide a neural substrate for representing acquired value and features of the predicted outcome during cue sampling, disruption of which could account for deficits in goal-directed behavior after damage to this system.



Dynamics of olfactory bulb input and output activity during odor stimulation in zebrafish

R. W. Friedrich and G. Laurent

J Neurophysiol  91  2658-69  (2004)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=14960561

The processing of odor-evoked activity in the olfactory bulb (OB) of zebrafish was studied by extracellular single unit recordings from the input and output neurons, i.e., olfactory receptor neurons (ORNs) and mitral cells (MCs), respectively. A panel of 16 natural amino acid odors was used as stimuli. Responses of MCs, but not ORNs, changed profoundly during the first few hundred milliseconds after response onset. In MCs, but not ORNs, the total evoked excitatory activity in the population was initially odor-dependent but subsequently converged to a common level. Hence, the overall population activity is regulated by network interactions in the OB. The tuning widths of both ORN and MC response profiles were similar and, on average, stable over time. However, when analyzed for individual neurons, MC response profiles could sharpen (excitatory response to fewer odors) or broaden (excitatory response to more odors), whereas ORN response profiles remained nearly unchanged. Several observations indicate that dynamic inhibition plays an important role in this remodeling. Finally, the reliability of odor identification based on MC population activity patterns improved over time, whereas odor identification based on ORN activity patterns was most reliable early in the odor response. These results demonstrate that several properties of MC, but not ORN, activity change during the initial phase of the odor response with important consequences for odor-encoding activity patterns. Furthermore, our data indicate that inhibitory interactions in the OB are important in dynamically shaping the activity of OB output neurons.



Interplay between local GABAergic interneurons and relay neurons generates gamma oscillations in the rat olfactory bulb

S. Lagier and A. Carleton and P. Lledo

J Neurosci  24  4382-92  (2004)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=15128852

Olfactory stimuli have been known for a long time to elicit oscillations in olfactory brain areas. In the olfactory bulb (OB), odors trigger synchronous oscillatory activity that is believed to arise from the coherent and rhythmic discharges of large numbers of neurons. These oscillations are known to take part in encoding of sensory information before their transfer to higher subcortical and cortical areas. To characterize the cellular mechanisms underlying gamma (30-80 Hz) local field potential (LFP) oscillations, we simultaneously recorded multiunit discharges, intracellular responses, and LFP in rat OB slices. We showed that a single and brief electrical stimulation of olfactory nerve elicited LFP oscillations in the mitral cell body layer lasting >1 sec. Both action potentials and subthreshold oscillations of mitral/tufted cells, the bulbar output neurons, were precisely synchronized with LFP oscillations. This synchronization arises from the interaction between output neurons and granule cells, the main population of local circuit inhibitory interneurons, through dendrodendritic synapses. Interestingly enough, the synchronization exerted by reciprocal synaptic interactions did not require action potentials initiated in granule cell somata. Finally, local application of a GABA(A) receptor antagonist at the mitral cell and external plexiform layers confirmed the exclusive role of the granule cell reciprocal synapses in generating the evoked oscillations. We concluded that interneurons located in the granule cell layer generate synaptic activity capable of synchronizing activity of output neurons by interacting with both their subthreshold and spiking activity.



Associative encoding in anterior piriform cortex versus orbitofrontal cortex during odor discrimination and reversal learning

M. R. Roesch and T. A. Stalnaker and G. Schoenbaum

Cereb Cortex  17  643-52  (2007)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=16699083

Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex (OFC). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. To test this hypothesis, we recorded from neurons in OFC and anatomically related parts of the anterior piriform cortex (APC) in rats, learning and reversing novel odor discriminations. Findings in OFC were similar to what we have reported previously, with nearly all the cue-selective neurons exhibiting substantial plasticity during learning and reversal. Also, many of the cue-selective neurons were originally responsive in anticipation of the outcomes early in learning, thereby providing a single-unit representation of the cue-outcome associations. Some of these features were also evident in firing activity in APC, including some plasticity across learning and reversal. However, APC neurons failed to reverse cue selectivity when the associated outcome was changed, and the cue-selective population did not include neurons that were active prior to outcome delivery. Thus, although representations in APC are substantially more associative than expected in a purely sensory region, they do appear to be somewhat more constrained by the sensory features of the odor cues than representations in downstream areas of OFC.



Separate encoding of identity and similarity of complex familiar odors in piriform cortex

M. Kadohisa and D. A. Wilson

Proc Natl Acad Sci U S A  103  15206-11  (2006)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17005727

Piriform cortical circuits are hypothesized to form perceptions from responses to specific odorant features, but the anterior piriform cortex (aPCX) and posterior piriform cortex (pPCX) differ markedly in their anatomical organization, differences that could lead to distinct roles in odor encoding. Here, we tested whether experience with a complex odorant mixture would modify encoding of the mixture and its components in aPCX and pPCX. Rats were exposed to an odorant mixture and its components in a go/no-go rewarded odor discrimination task. After reaching behavioral performance criterion, single-unit recordings were made from the aPCX and pPCX in these rats and in odor-naïve, control, urethane-anesthetized rats. After odor experience, aPCX neurons were more narrowly tuned to the test odorants, and there was a decorrelation in aPCX population responses to the mixture and its components, suggesting a more distinct encoding of the familiar mixture from its components. In contrast, pPCX neurons were more broadly tuned to the familiar odorants, and pPCX population responses to the mixture and its components became more highly correlated, suggesting a pPCX encoding of similarity between familiar stimuli. The results suggest aPCX and pPCX play different roles in the processing of familiar odors and are consistent with an experience-dependent encoding (perceptual learning) of synthetic odorant identity in aPCX and an experience-dependent encoding of odor similarity or odor quality in pPCX.



Faithful representation of stimuli with a population of integrate-and-fire neurons

A. A. Lazar and E. A. Pnevmatikakis

Neural Comput  20  2715-44  (2008)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=18533815

We consider a formal model of stimulus encoding with a circuit consisting of a bank of filters and an ensemble of integrate-and-fire neurons. Such models arise in olfactory systems, vision, and hearing. We demonstrate that bandlimited stimuli can be faithfully represented with spike trains generated by the ensemble of neurons. We provide a stimulus reconstruction scheme based on the spike times of the ensemble of neurons and derive conditions for perfect recovery. The key result calls for the spike density of the neural population to be above the Nyquist rate. We also show that recovery is perfect if the number of neurons in the population is larger than a threshold value. Increasing the number of neurons to achieve a faithful representation of the sensory world is consistent with basic neurobiological thought. Finally we demonstrate that in general, the problem of faithful recovery of stimuli from the spike train of single neurons is ill posed. The stimulus can be recovered, however, from the information contained in the spike train of a population of neurons.



Synaptic learning rules and sparse coding in a model sensory system

L. A. Finelli and S. Haney and M. Bazhenov and M. Stopfer and T. J. Sejnowski

PLoS Comput Biol  4  e1000062  (2008)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=18421373

Neural circuits exploit numerous strategies for encoding information. Although the functional significance of individual coding mechanisms has been investigated, ways in which multiple mechanisms interact and integrate are not well understood. The locust olfactory system, in which dense, transiently synchronized spike trains across ensembles of antenna lobe (AL) neurons are transformed into a sparse representation in the mushroom body (MB; a region associated with memory), provides a well-studied preparation for investigating the interaction of multiple coding mechanisms. Recordings made in vivo from the insect MB demonstrated highly specific responses to odors in Kenyon cells (KCs). Typically, only a few KCs from the recorded population of neurons responded reliably when a specific odor was presented. Different odors induced responses in different KCs. Here, we explored with a biologically plausible model the possibility that a form of plasticity may control and tune synaptic weights of inputs to the mushroom body to ensure the specificity of KCs' responses to familiar or meaningful odors. We found that plasticity at the synapses between the AL and the MB efficiently regulated the delicate tuning necessary to selectively filter the intense AL oscillatory output and condense it to a sparse representation in the MB. Activity-dependent plasticity drove the observed specificity, reliability, and expected persistence of odor representations, suggesting a role for plasticity in information processing and making a testable prediction about synaptic plasticity at AL-MB synapses.



Characterization and coding of behaviorally significant odor mixtures

J. A. Riffell and H. Lei and T. A. Christensen and J. G. Hildebrand

Curr Biol  19  335-40  (2009)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=19230669

For animals to execute odor-driven behaviors, the olfactory system must process complex odor signals and maintain stimulus identity in the face of constantly changing odor intensities [1-5]. Surprisingly, how the olfactory system maintains identity of complex odors is unclear [6-10]. We took advantage of the plant-pollinator relationship between the Sacred Datura (Datura wrightii) and the moth Manduca sexta[11, 12] to determine how olfactory networks in this insect's brain represent odor mixtures. We combined gas chromatography and neural-ensemble recording in the moth's antennal lobe to examine population codes for the floral mixture and its fractionated components. Although the floral scent of D. wrightii comprises at least 60 compounds, only nine of those elicited robust neural responses. Behavioral experiments confirmed that these nine odorants mediate flower-foraging behaviors, but only as a mixture. Moreover, the mixture evoked equivalent foraging behaviors over a 1000-fold range in dilution, suggesting a singular percept across this concentration range. Furthermore, neural-ensemble recordings in the moth's antennal lobe revealed that reliable encoding of the floral mixture is organized through synchronized activity distributed across a population of glomerular coding units, and this timing mechanism may bind the features of a complex stimulus into a coherent odor percept.



Bidirectional processing in the olfactory-limbic axis during olfactory behavior

L. M. Kay and W. J. Freeman

Behav Neurosci  112  541-53  (1998)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=9676972

Field potentials were recorded simultaneously from the olfactory bulb (OB), prepyriform cortex (PPC), entorhinal cortex (EC), and dentate gyrus (DG) of rats trained to respond to appetitively reinforced odors. Preafferent anticipatory events in the beta band (12-35 Hz) suggest transmission from EC to OB before the odorant stimulus. Gamma band (35-120 Hz) power in olfactory regions is significantly reduced during stimulus presentation as compared with high values during preafferent expectation. High coherence of OB and PPC gamma activity during the preodorant control period is interrupted before the stimulus and is followed by increased gamma coherence among OB, EC, and DG. These results suggest that olfactory perceptual processing is bidirectional and covers a wide frequency range.



Asymmetric sigmoid non-linearity in the rat olfactory system

F. H. Eeckman and W. J. Freeman

Brain Res  557  13-21  (1991)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=1747747

The statistical relationship between multi-unit spike activity and simultaneously recorded local dendritic field potentials in the olfactory system of the waking rat was studied with chronically placed electrodes. The relationship had the form of a sigmoid increase in axonal firing probability conditional on the amplitude of dendritic potentials. These data were fitted with an asymmetric sigmoid curve previously derived from the Hodgkin-Huxley equations. The curve was fitted using non-linear regression to optimize its parameter: the maximal firing rate. The maximal rate also gave the steepness of the slope of the sigmoid. Pulse trains were recorded from excitatory and inhibitory neurons in the olfactory cortex (including the anterior olfactory nucleus, the prepyriform cortex and the lateral entorhinal area) as identified by the phase relations of the pulse probability and the dendritic potentials, and from the excitatory neurons in the bulb (the inhibitory granule cells do not give extracellularly detectable action potentials). All these neurons are known to interact in disynaptic negative feedback loops giving rise to oscillations. The same sigmoid function fit the data from both types of neurons in all locations. The curves for neurons in all parts of the olfactory cortex had a 3-fold higher slope and maximal value than the curves from bulbar neurons. The significances of this difference and of the asymmetric sigmoid are discussed in terms of models for olfactory oscillatory dynamics and pattern recognition.



Correlations between unit firing and EEG in the rat olfactory system

F. H. Eeckman and W. J. Freeman

Brain Res  528  238-44  (1990)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=2271924

The olfactory EEG of awake animals displays oscillatory bursts of activity in the gamma- (30-100 Hz) range. The bursts are correlated with inflow of air over the receptor layer in the nose. None of the inputs to the cortices that display these oscillations carries periodic signals in the gamma-range. Thus these bursts are generated locally, either by neuronal feedback interactions or by coupling of oscillatory neurons. In the first case if the oscillations are generated by negative feedback, then two classes of cells must exist: excitatory neurons and inhibitory neurons with the same frequency of oscillation but with a quarter cycle phase lag by the inhibitory cells from the excitatory cells. On the other hand, if the EEG's result from coupling of cells that are intrinsically oscillatory, there should be a broad but monomodal distribution of phase values. In order to determine the origin of these bursts, we performed simultaneous recordings of EEG and multi-unit spikes in the 4 parts of the olfactory system (olfactory bulb, anterior olfactory nucleus, prepyriform cortex and lateral entorhinal area) of awake and motivated rats. For each sample, the EEG and the multi-unit spikes were recorded from the same local neighborhood. The multi-unit electrode recorded pulses from the principal output neurons of the respective cortical areas. In all locations tested, the oscillations in pulse probabilities of firing were found to have the same frequency as the dominant EEG frequency. In all 4 structures two sets of cells were found. One set displayed pulses in phase with the EEG and the other set displayed pulses that led or lagged the EEG by approximately 1/4 cycle. These data confirm the negative feedback interaction model rather than the coupled oscillator model for the generation of the bursts in the olfactory system. The relevance of these findings to other cortical systems, in casu the visual cortex is discussed.



Spatial EEG correlates of nonassociative and associative olfactory learning in rabbits

K. A. Grajski and W. J. Freeman

Behav Neurosci  103  790-804  (1989)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=2765184

Recent studies have shown that spatially distributed olfactory bulbar activity correlates with odor-specific behavioral responding (Coopersmith \& Leon, 1984; Freeman \& Grajski, 1987; Freeman \& Schneider, 1982; Freeman \& Viana di Prisco, 1986; Grajski, Breiman, Viana di Prisco, \& Freeman, 1986; Gray, Freeman, \& Skinner, 1986; Sullivan \& Leon, 1986; Viana di Prisco \& Freeman, 1985). The present studies established olfactory bulbar spatial electroencephalogram (EEG) correlates of nonassociative and associative learning in odorant stimulation in rabbits. Behavior was quantified by measuring magnitude and probability of the sniff response. It was shown that (a) olfactory bulbar spatial EEG amplitude patterns do not simply reflect odor (peripheral) stimulation, (b) repeated presentations of a nonreinforced odor initially reveal a transient EEG pattern change but the pattern change does not recur after the subject has habituated to the odor, and (c) repeated presentations of a reinforced odor (mild cutaneous shock), with a second nonreinforced odor serving as a control, reveal that coexisting, odor-specific spatial EEG amplitude patterns emerge with the acquisition of differential behavioral responding.



Brain neural activity patterns yielding numbers are operators, not representations

W. J. Freeman and R. Kozma

Behav Brain Sci  32  336-7; discussion 356-73  (2009)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=19712512

We contrapose computational models using representations of numbers in parietal cortical activity patterns (abstract or not) with dynamic models, whereby prefrontal cortex (PFC) orchestrates neural operators. The neural operators under PFC control are activity patterns that mobilize synaptic matrices formed by learning into textured oscillations we observe through the electroencephalogram from the scalp (EEG) and the electrocorticogram from the cortical surface (ECoG). We postulate that specialized operators produce symbolic representations existing only outside of brains.



Olfactory learning-induced long-lasting enhancement of descending and ascending synaptic transmission to the piriform cortex

Y. Cohen and I. Reuveni and E. Barkai and M. Maroun

J Neurosci  28  6664-9  (2008)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=18579740

Learning of a particularly difficult olfactory-discrimination (OD) task results in acquisition of rule learning. This remarkable enhancement in learning capability is accompanied by long-term enhancement of synaptic connectivity between piriform cortex (PC) pyramidal neurons. Because successful performance in the OD task requires integration of information about the identity and also about the reward value of odors, it is likely that a higher-order brain area would also be involved in rule learning acquisition and maintenance. The anterior PC (APC) receives a strong ascending input from the olfactory bulb, carrying information regarding olfactory cues in the environment. It also receives substantial descending input from the orbitofrontal cortex (OFC), which is thought to play an important role in encoding the predictive value of odor stimuli. Using in vivo recordings of evoked field postsynaptic potentials, we characterized the physiological properties of projections to APC from the OFC and examined whether descending and ascending synaptic inputs to the piriform cortex are modified after OD learning. We show that enhanced learning capability is accompanied by long-term enhancement of synaptic transmission in both the descending and ascending inputs. Long-term synaptic enhancement is not accompanied by modifications in paired-pulse facilitation, indicating that such modifications are likely postsynaptic. Predisposition for long-term potentiation induction was affected by previous learning, and surprisingly also by previous exposure to the odors and training apparatus. These data suggest that enhanced connectivity between the APC and its input sources is required for OD rule learning.



Upregulation of neurotrophic factors selectively in frontal cortex in response to olfactory discrimination learning

A. Naimark and E. Barkai and M. A. Matar and Z. Kaplan and N. Kozlovsky and H. Cohen

Neural Plast  2007  13427  (2007)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17710248

We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks.



CAMKII activation is not required for maintenance of learning-induced enhancement of neuronal excitability

O. Liraz and K. Rosenblum and E. Barkai

PLoS One  4  e4289  (2009)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=19172997

Pyramidal neurons in the piriform cortex from olfactory-discrimination trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the post-burst after-hyperpolarization (AHP) which is generated by repetitive spike firing. AHP reduction is due to decreased conductance of a calcium-dependent potassium current, the sI(AHP). We have previously shown that learning-induced AHP reduction is maintained by persistent protein kinase C (PKC) and extracellular regulated kinase (ERK) activation. However, the molecular machinery underlying this long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the CaMKII, which is known to be crucial in learning, memory and synaptic plasticity processes, is instrumental for the maintenance of learning-induced AHP reduction. KN93, that selectively blocks CaMKII autophosphorylation at Thr286, reduced the AHP in neurons from trained and control rat to the same extent. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls remained. Accordingly, the level of activated CaMKII was similar in pirifrom cortex samples taken form trained and control rats. Our data show that although CaMKII modulates the amplitude of AHP of pyramidal neurons in the piriform cortex, its activation is not required for maintaining learning-induced enhancement of neuronal excitability.



Reduced synaptic facilitation between pyramidal neurons in the piriform cortex after odor learning

D. Saar and Y. Grossman and E. Barkai

J Neurosci  19  8616-22  (1999)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=10493761

Learning-related cellular modifications were studied in the rat piriform cortex after operand conditioning. Rats were trained to discriminate positive cues in pairs of odors. In one experimental paradigm, rats were trained to memorize 35-50 pairs of odors ("extensive training"). In another paradigm, training was continued only until rats acquired the rule of the task, usually after learning the first two pairs of odors ("short training"). "Pseudotrained" and "naive" rats served as controls. We have previously shown that "rule learning" of this task was accompanied by reduced spike afterhyperpolarization in pyramidal neurons in brain slices of the piriform cortex. In the present study, synaptic inputs to the same cells were examined. Pairs of electrical stimuli applied to the intrinsic fibers that interconnect layer II pyramidal neurons revealed significant reduction in paired-pulse facilitation (PPF) in this pathway even after short training. PPF in shortly trained rats was reduced to the same extent as in extensively trained rats. PPF reduction did not result from modification of membrane properties in the postsynaptic cells, change in postsynaptic inhibition, or impairment of the facilitation mechanism. Extracellular field potential recordings showed enhanced synaptic transmission in these synapses. The reduction in PPF became apparent only 3 d after task acquisition and returned to control value 5 d later. PPF evoked by stimulating the afferent fibers to the same neurons was increased 1 d after training for 2 d. We suggest that the transient enhancement in connectivity in the intrinsic pathway is related to the enhanced learning capability and not to memory for specific odors, which lasts for weeks.



Cellular correlates of olfactory learning in the rat piriform cortex

E. Barkai and D. Saar

Rev Neurosci  12  111-20  (2001)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=11392453

This review describes research that combines cellular physiology with behavioral neuroscience, to study the cellular mechanisms underlying learning and memory in the mammalian brain. Rats were trained with an olfactory conditioning paradigm, in which they had to memorize odors in order to be rewarded with drinking water. Such training results in rule learning, which enables enhanced acquisition of odor memory. Training results in the following learning-related physiological modifications in intrinsic and synaptic properties in olfactory (piriform) cortex pyramidal neurons: 1. increased neuronal excitability, indicated by reduced afterhyperpolarization, and 2. increased synaptic transmission, indicated by reduced paired-pulse facilitation. These modifications are correlated to enhanced learning capability rather than to storage of memory for specific odors. In addition, using a different paradigm of odor-training, it is shown that NMDA and betra-adrenergic receptors are involved at different stages of long-term memory consolidation.



Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task

E. van Duuren and F. A. N. Escámez and R. N. J. M. A. Joosten and R. Visser and A. B. Mulder and C. M. A. Pennartz

Learn Mem  14  446-56  (2007)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17562896

The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural activity was recorded during an olfactory discrimination "go"/"no-go" task in which five different odor stimuli were predictive for various amounts of reward or an aversive reinforcer. Neural correlates related to both actual and expected reward magnitude were observed. Responses related to reward expectation occurred during the execution of the behavioral response toward the reward site and within a waiting period prior to reinforcement delivery. About one-half of these neurons demonstrated differential firing toward the different reward sizes. These data provide new and strong evidence that reward expectancy, regardless of reward magnitude, is coded by neurons of the rat OBFc, and are indicative for representation of quantitative information concerning expected reward. Moreover, neural correlates of reward expectancy appear to be distributed across both motor and nonmotor phases of the task.



Neural correlates of olfactory recognition memory in the rat orbitofrontal cortex

S. J. Ramus and H. Eichenbaum

J Neurosci  20  8199-208  (2000)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=11050143

The orbitofrontal cortex (OF) is strongly and reciprocally connected with the perirhinal (PR) and entorhinal areas of the medial temporal lobe and plays an important role in odor recognition memory. This study characterized firing patterns of single neurons in the OF of rats performing a continuous odor-guided delayed nonmatch to sample (DNMS) task. Most OF neurons fired in association with one or more task events, including the initiation of trials, the sampling of odor stimuli, and the consumption of rewards. OF neurons also exhibited sustained odor-selective activity during the memory delay, and a large proportion of OF cells had odor-specific enhanced or suppressed responses on stimulus repetition. Most OF neurons were activated during several task events, or associated with complex behavioral states. The incidence of cells that fired in association with the critical match/non-match judgement was increased as the DNMS rule was learned, and was higher in OF than in perirhinal and entorhinal cortex. Furthermore, the classification of match and nonmatch trials was correlated with accuracy in performance of that judgement. These findings are consistent with the view that OF is a high order association cortex that plays a role both in the memory representations for specific stimuli and in the acquisition and application of task rules.



Information coding in the rodent prefrontal cortex. II. Ensemble activity in orbitofrontal cortex

G. Schoenbaum and H. Eichenbaum

J Neurophysiol  74  751-62  (1995)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=7472379

1. Neural activity was recorded from the orbitofrontal cortex (OF) of rats performing an eight-odor discrimination task that included predictable associations between particular odor pairs. A modified linear discriminant analysis was employed to characterize the population response in each trial of the task as a point in an N-dimensional activity space with the firing rate of each cell in the population represented on one of the N dimensions. The ability of the ensemble to discriminate among conditions of a variable was reflected in the tendency of population responses to cluster together in this activity space for repetitions of a given condition. We assessed coding of several variables describing the period of odor sampling, focusing on aspects of current, past, and future events reflected in single-neuron firing patterns, in ensembles composed of 22-138 cells active during the period when the rats sampled the discriminative stimulus in each trial. 2. OF ensembles performed well at discriminating variables with relevance to task demands represented in single-neuron firing patterns, specifically the physical attributes and assigned reward contingency of the current odor as well as the expectation of reward in the following trial that could be inferred from the predictable associations between particular pairs of odors. OF ensembles were able to correctly identify the identity and assigned reward contingency of the current odor in up to 52\% (chance = 12.5\%) and 99\% (chance = 50\%) of all trials, respectively, such that the observed behavioral performance required a population of 5,364 odor-responsive cells in the case of odor identity and only 40 cells in the case of valence. Expectations regarding upcoming rewards based on both assigned response contingency and associations between particular pairs of odors were correctly classified in up to 67\% (chance = 20\%) of all trials such that the observed level of behavioral performance required a population of 3,169 cells. 3. Other information represented in the single-neuron firing patterns, such as the identity and reward contingency of the preceding odor and specific odor-odor associations, was poorly encoded by OF ensembles. Thus neural ensembles in OF may represent only some of the information reflected in single-neuron activity. Stable coding of only the most useful and relevant information by the ensemble might emerge from the tuning properties of single neurons under the influence of the task at hand, producing in the well-trained animal the observed pattern of broad and diverse coding by single neurons and selective, task-relevant coding by neural ensembles in OF.



Information coding in the rodent prefrontal cortex. {I}. {S}ingle-neuron activity in orbitofrontal cortex compared with that in pyriform cortex.

G. Schoenbaum and H. Eichenbaum

J Neurophysiol  74  733-50  (1995)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=7472378

1. Extracellular spike activity was recorded from 1,942 single neurons in orbitofrontal cortex (OF) and 591 single neurons in pyriform cortex (PIR) over multiple sessions in rats performing an eight-odor discrimination task in which the stimulus sequence contained predictable associations between particular odor pairs. Neural firing patterns were examined in relation to task events in the current trial and variables associated with current sensory processing, events of recent past trials, and long-term associations involving the odor cues. 2. Overall, 34\% of single neurons in OF and 30\% of single neurons in PIR fired selectively during one or more salient trial events including trial initiation, odor sampling, performance of the discriminative response, and water consumption. The activity of other cells recorded in OF (13\%) and PIR (10\%) was suppressed for the duration of each trial. Although the proportion of some cell types differed between the two areas, the firing patterns of OF and PIR neurons were qualitatively indistinguishable. 3. Firing during odor sampling and the discriminative response was influenced by the identity of the current odor. Some cells fired selectively to a single odor, but most cells were coarsely tuned such that they fired to several of the eight odors to differing degrees consistent with previous reports. Considerable odor coding was observed in both OF and PIR. 4. Firing during trial initiation and odor sampling was also influenced by the identity and reward association of the odor presented in the immediately preceding trial. The influence of past odor identity and valence was observed in both OF and PIR. 5. Firing during trial events was also influenced by the acquired associations between odors and their assigned reward contingencies and between pairs of odors involved in predictive relationships. The reward valence of the current odor significantly influenced firing during odor sampling and the discriminative response; some cells responded preferentially to rewarded odors and others to nonrewarded odors. Firing during trial initiation and odor sampling reflected whether or not the odor in the current trial had been predicted by the odor in the preceding trial. In addition, firing during odor sampling reflected the expectation of reward in the following trial that could be inferred from the predictable associations between odors. Each of these properties was observed in both OF and PIR. 6. The findings in OF were consistent with the view that prefrontal subdivisions mediate the temporal organization of complex behaviors within specific informational domains. OF appears to be concerned with the specific domain of olfaction.(ABSTRACT TRUNCATED AT 400 WORDS)



Quantitative fine-structural analysis of olfactory cortical synapses.

T. Schikorski and C. Stevens

Proc Natl Acad Sci U S A  96  4107-12  (1999)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=10097171

To determine the extent to which hippocampal synapses are typical of those found in other cortical regions, we have carried out a quantitative analysis of olfactory cortical excitatory synapses, reconstructed from serial electron micrograph sections of mouse brain, and have compared these new observations with previously obtained data from hippocampus. Both superficial and deep layer I olfactory cortical synapses were studied. Although individual synapses in each of the areas-CA1 hippocampus, olfactory cortical layer Ia, olfactory cortical area Ib-might plausibly have been found in any of the other areas, the average characteristics of the three synapse populations are distinct. Olfactory cortical synapses in both layers are, on average, about 2.5 times larger than their hippocampal counterparts. The layer Ia olfactory cortical synapses have fewer synaptic vesicles than do the layer Ib synapses, but the absolute number of vesicles docked to the active zone in the layer Ia olfactory cortical synapses is about equal to the docked vesicle number in the smaller hippocampal synapses. As would be predicted from studies on hippocampus that relate paired-pulse facilitation to the number of docked vesicles, the synapses in layer 1a exhibit facilitation, whereas the ones in layer 1b do not. Although hippocampal synapses provide as a good model system for central synapses in general, we conclude that significant differences in the average structure of synapses from one cortical region to another exist, and this means that generalizations based on a single synapse type must be made with caution.



Neural encoding of rapidly fluctuating odors.

M. N. Geffen and B. M. Broome and G. Laurent and M. Meister

Neuron  61  570--586  (2009)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=19249277

Olfactory processing in the insect antennal lobe is a highly dynamic process, yet it has been studied primarily with static step stimuli. To approximate the rapid odor fluctuations encountered in nature, we presented flickering "white-noise" odor stimuli to the antenna of the locust and recorded spike trains from antennal lobe projection neurons (PNs). The responses varied greatly across PNs and across odors for the same PN. Surprisingly, this diversity across the population was highly constrained, and most responses were captured by a quantitative model with just 3 parameters. Individual PNs were found to communicate odor information at rates up to approximately 4 bits/s. A small group of PNs was sufficient to provide an accurate representation of the dynamic odor time course, whose quality was maximal for fluctuations of frequency approximately 0.8 Hz. We develop a simple model for the encoding of dynamic odor stimuli that accounts for many prior observations on the population response.



Fast odor learning improves reliability of odor responses in the locust antennal lobe.

M. Bazhenov and M. Stopfer and T. J. Sejnowski and G. Laurent

Neuron  46  483--492  (2005)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=15882647

Recordings in the locust antennal lobe (AL) reveal activity-dependent, stimulus-specific changes in projection neuron (PN) and local neuron response patterns over repeated odor trials. During the first few trials, PN response intensity decreases, while spike time precision increases, and coherent oscillations, absent at first, quickly emerge. We examined this "fast odor learning" with a realistic computational model of the AL. Activity-dependent facilitation of AL inhibitory synapses was sufficient to simulate physiological recordings of fast learning. In addition, in experiments with noisy inputs, a network including synaptic facilitation of both inhibition and excitation responded with reliable spatiotemporal patterns from trial to trial despite the noise. A network lacking fast plasticity, however, responded with patterns that varied across trials, reflecting the input variability. Thus, our study suggests that fast olfactory learning results from stimulus-specific, activity-dependent synaptic facilitation and may improve the signal-to-noise ratio for repeatedly encountered odor stimuli.