NSci 3102 2009 Readings

Cell communication mechanisms in the vertebrate retina the proctor lecture.
R. F. Miller
Invest Ophthalmol Vis Sci 49 5184--5198 (2008 Dec)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=19036997

The vertebrate retina has a unique position within the panoply of the nervous system networks: Our understanding of its complex circuitry of interacting neurons and glia has become the gold standard of our current knowledge of network operations. This presentation is about work from my laboratory that contributed to some of the concepts that support our contemporary views of the functional retina. Early in the pursuit of retinal function, a vital issue was that of understanding the synaptic mechanisms and neurotransmitters required for information to flow from the photoreceptors to the ganglion cells. My research contributions to this effort include the discovery of inhibition and the GABA and glycine modes of inhibitory mechanisms. Our work on inhibition was followed by the discovery of the APB (mGluR6) receptor of On bipolars, the first metabotropic glutamate receptor described in the nervous system. This finding was followed by a body of work carried out in salamander and rabbit retinas on the pathways of glutamatergic excitation revealed through the use of agonists and antagonists of increasing selectivity. We separated sign-conserving from sign-inverting responses in the outer retina and provided compelling evidence that bipolars, like photoreceptors, had a glutamatergic mode of neurotransmission. We identified NMDA (N-methyl-d-aspartate) and KA (kainic acid)/AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors in amacrine and ganglion cells and revealed that both receptor classes are activated by light. Additional studies on neuropeptides illustrated how many of these, including substance P, somatostatin, and neurotensin have actions such that they should be considered major neuromodulators in the retina. My laboratory also made significant contributions to structure-function relationships and mechanisms of glial-neuronal interactions.

Anticipation of moving stimuli by the retina.
M. J. n. Berry and I. H. Brivanlou and T. A. Jordan and M. Meister
Nature 398 334--338 (1999 Mar 25)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=10192333

A flash of light evokes neural activity in the brain with a delay of 30-100 milliseconds, much of which is due to the slow process of visual transduction in photoreceptors. A moving object can cover a considerable distance in this time, and should therefore be seen noticeably behind its actual location. As this conflicts with everyday experience, it has been suggested that the visual cortex uses the delayed visual data from the eye to extrapolate the trajectory of a moving object, so that it is perceived at its actual location. Here we report that such anticipation of moving stimuli begins in the retina. A moving bar elicits a moving wave of spiking activity in the population of retinal ganglion cells. Rather than lagging behind the visual image, the population activity travels near the leading edge of the moving bar. This response is observed over a wide range of speeds and apparently compensates for the visual response latency. We show how this anticipation follows from known mechanisms of retinal processing.

Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual system.
C. Pfeiffenberger and J. Yamada and D. A. Feldheim
J Neurosci 26 12873--12884 (2006 Dec 13)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=17167078

The development of topographic maps in the primary visual system is thought to rely on a combination of EphA/ephrin-A interactions and patterned neural activity. Here, we characterize the retinogeniculate and retinocollicular maps of mice mutant for ephrins-A2, -A3, and -A5 (the three ephrin-As expressed in the mouse visual system), mice mutant for the beta2 subunit of the nicotinic acetylcholine receptor (that lack early patterned retinal activity), and mice mutant for both ephrin-As and beta2. We also provide the first comprehensive anatomical description of the topographic connections between the retina and the dorsal lateral geniculate nucleus. We find that, although ephrin-A2/A3/A5 triple knock-out mice have severe mapping defects in both projections, they do not completely lack topography. Mice lacking beta2-dependent retinal activity have nearly normal topography but fail to refine axonal arbors. Mice mutant for both ephrin-As and beta2 have synergistic mapping defects that result in a near absence of map in the retinocollicular projection; however, the retinogeniculate projection is not as severely disrupted as the retinocollicular projection is in these mutants. These results show that ephrin-As and patterned retinal activity act together to establish topographic maps, and demonstrate that midbrain and forebrain connections have a differential requirement for ephrin-As and patterned retinal activity in topographic map development.

Two mechanisms for transducer adaptation in vertebrate hair cells.
J. R. Holt and D. P. Corey
Proc Natl Acad Sci U S A 97 11730--11735 (2000)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=11050202

Deflection of the hair bundle atop a sensory hair cell modulates the open probability of mechanosensitive ion channels. In response to sustained deflections, hair cells adapt. Two fundamentally distinct models have been proposed to explain transducer adaptation. Both models support the notion that channel open probability is modulated by calcium that enters via the transduction channels. Both also suggest that the primary effect of adaptation is to shift the deflection-response [I(X)] relationship in the direction of the applied stimulus, thus maintaining hair bundle sensitivity. The models differ in several respects. They operate on different time scales: the faster on the order of a few milliseconds or less and the slower on the order of 10 ms or more. The model proposed to explain fast adaptation suggests that calcium enters and binds at or near the transduction channels to stabilize a closed conformation. The model proposed to explain the slower adaptation suggests that adaptation is mediated by an active, force-generating process that regulates the effective stimulus applied to the transduction channels. Here we discuss the evidence in support of each model and consider the possibility that both may function to varying degrees in hair cells of different species and sensory organs.

Incremental training increases the plasticity of the auditory space map in adult barn owls.
B. A. Linkenhoker and E. I. Knudsen
Nature 419 293-6 (2002)
http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?cmd=prlinks\&dbfrom=pubmed\&retmode=ref\&id=12239566

The plasticity in the central nervous system that underlies learning is generally more restricted in adults than in young animals. In one well-studied example, the auditory localization pathway has been shown to be far more limited in its capacity to adjust to abnormal experience in adult than in juvenile barn owls. Plasticity in this pathway has been induced by exposing owls to prismatic spectacles that cause a large, horizontal shift of the visual field. With prisms, juveniles learn new associations between auditory cues, such as interaural time difference (ITD), and locations in visual space, and acquire new neurophysiological maps of ITD in the optic tectum, whereas adults do neither. Here we show that when the prismatic shift is experienced in small increments, maps of ITD in adults do change adaptively. Once established through incremental training, new ITD maps can be reacquired with a single large prismatic shift. Our results show that there is a substantially greater capacity for plasticity in adults than was previously recognized and highlight a principled strategy for tapping this capacity that could be applied in other areas of the adult central nervous system.

Adaptive changes of the vestibulo-ocular reflex in flatfish are achieved by reorganization of central nervous pathways.
W. Graf and R. Baker
Science 221 777--779 (1983)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=6603656

Flatfish provide a natural model for the study of adaptive changes in the vestibulo-ocular reflex system. During metamorphosis their vestibular and oculomotor coordinate systems undergo a 90 degree relative displacement. As a result, during swimming movements different types of compensatory eye movements are produced before and after metamorphosis by the same vestibular stimulation. Intracellular staining of central nervous connections in the flatfish with horseradish peroxidase revealed that in postmetamorphic fish secondary horizontal semicircular canal neurons contact vertical eye muscle motoneuron pools on both sides of the brain via pathways that are absent in all other vertebrates studied.

Specificity of monosynaptic connections from thalamus to visual cortex.
R. Reid and J. Alonso
Nature 378 281-4 (1995)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=7477347

In cortical area 17 of the cat, simple receptive fields are arranged in elongated subregions that respond best to bright (on) or dark (off) oriented contours, whereas the receptive fields of their thalamic inputs have a concentric on and off organization. This dramatic transformation suggests that there are specific rules governing the connections made between thalamic and cortical neurons (see ref. 4). Here we report a study of these rules in which we recorded from thalamic (lateral geniculate nucleus; LGN) and cortical neurons simultaneously and related their receptive fields to their connectivity, as measured by cross-correlation analysis. The probability of finding a monosynaptic connection was high when a geniculate receptive field was superimposed anywhere over an elongated simple-cell subregion of the same signature (on or off). However, 'inappropriate' connections from geniculate cells of the opposite receptive field signature were extremely rare. Together, these findings imply that the outline of the elongated, simple receptive field, and thus of cortical orientation selectivity, is laid down at the level of the first synapse from the thalamic afferents.

The role of visual experience in the development of columns in cat visual cortex.
M. Crair and D. Gillespie and M. Stryker
Science 279 566-70 (1998)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9438851

The role of experience in the development of the cerebral cortex has long been controversial. Patterned visual experience in the cat begins when the eyes open about a week after birth. Cortical maps for orientation and ocular dominance in the primary visual cortex of cats were found to be present by 2 weeks. Early pattern vision appeared unimportant because these cortical maps developed identically until nearly 3 weeks of age, whether or not the eyes were open. The naive maps were powerfully dominated by the contralateral eye, and experience was needed for responses to the other eye to become strong, a process unlikely to be strictly Hebbian. With continued visual deprivation, responses to both eyes deteriorated, with a time course parallel to the well-known critical period of cortical plasticity. The basic structure of cortical maps is therefore innate, but experience is essential for specific features of these maps, as well as for maintaining the responsiveness and selectivity of cortical neurons.

Linked target selection for saccadic and smooth pursuit eye movements.
J. L. Gardner and S. G. Lisberger
J Neurosci 21 2075-84 (2001)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11245691

In natural situations, motor activity must often choose a single target when multiple distractors are present. The present paper asks how primate smooth pursuit eye movements choose targets, by analysis of a natural target-selection task. Monkeys tracked two targets that started 1.5 degrees eccentric and moved in different directions (up, right, down, and left) toward the position of fixation. As expected from previous results, the smooth pursuit before the first saccade reflected a vector average of the responses to the two target motions individually. However, post-saccadic smooth eye velocity showed enhancement that was spatially selective for the motion at the endpoint of the saccade. If the saccade endpoint was close to one of the two targets, creating a targeting saccade, then pursuit was selectively enhanced for the visual motion of that target and suppressed for the other target. If the endpoint landed between the two targets, creating an averaging saccade, then post-saccadic smooth eye velocity also reflected a vector average of the two target motions. Saccades with latencies >200 msec were almost always targeting saccades. However, pursuit did not transition from vector-averaging to target-selecting until the occurrence of a saccade, even when saccade latencies were >300 msec. Thus, our data demonstrate that post-saccadic enhancement of pursuit is spatially selective and that noncued target selection for pursuit is time-locked to the occurrence of a saccade. This raises the possibility that the motor commands for saccades play a causal role, not only in enhancing visuomotor transmission for pursuit but also in choosing a target for pursuit.

Neural mechanisms for forming a perceptual decision.
C. Salzman and W. Newsome
Science 264 231-7 (1994)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8146653

Cognitive and behavioral responses to environmental stimuli depend on an evaluation of sensory signals within the cerebral cortex. The mechanism by which this occurs in a specific visual task was investigated with a combination of physiological and psychophysical techniques. Rhesus monkeys discriminated among eight possible directions of motion while directional signals were manipulated in visual area MT. One directional signal was generated by a visual stimulus and a second signal was introduced by electrically stimulating neurons that encoded a specific direction of motion. The decisions made by the monkeys in response to the two signals allowed a distinction to be made between two possible mechanisms for interpreting directional signals in MT. The monkeys tended to cast decisions in favor of one or the other signal, indicating that the signals exerted independent effects on performance and that an interactive mechanism such as vector averaging of the two signals was not operative. Thus, the data suggest a mechanism in which monkeys chose the direction encoded by the largest signal in the representation of motion direction, a 'winner-take-all' decision process.

The Hymenopteran Skylight Compass: Matched Filtering and Parallel Coding
R. Wehner
J Exp Biol 146 63-85 (1989)
http://jeb.biologists.org/cgi/content/abstract/146/1/63

In deriving compass information from the pattern of polarized light in the sky (celestial e-vector pattern), hymenopteran insects like bees and ants accomplish a truly formidable task. Theoretically, one could solve the task by going back to first principles and using spherical geometry to compute the exact position of the sun from single patches of polarized skylight. The insect, however, does not resort to such computationally demanding solutions. Instead, during its evolutionary history, it has incorporated the fundamental spatial properties of the celestial pattern of polarization in the very periphery of its nervous system, the photoreceptor layer. There, in a specialized part of the retina (POL area), the analyser (microvillar) directions of the photoreceptors are arranged in a way that mimics the e-vector pattern in the sky (matched filtering). When scanning the sky, i.e. sweeping its matched array of analysers across the celestial e-vector pattern, the insect experiences peak responses of summed receptor outputs whenever it is aligned with the symmetry plane of the sky, which includes the solar meridian, the perpendicular from the sun to the horizon. Hence, the insect uses polarized skylight merely as a means of determining the symmetry plane of the polarization pattern, and must resort to other visual subsystems to deal with the remaining aspects of the compass problem (parallel coding). The more general message to be derived from these results is that in small brains sensory coding consists of adapting the peripheral rather than the central networks of the brain to the functional properties of the particular task to be solved. The matched peripheral networks translate the sensory information needed for performing a particular mode of behaviour into a neuronal code that can easily be understood by well-established, unspecialized central circuits. This principle of sensory coding implies that the peripheral parts of the nervous system exhibit higher evolutionary plasticity than the more central ones. Furthermore, it is reminiscent of what one observes at the cellular level of information processing, where the membrane-bound receptor molecules are specialized for particular molecular signals, but the subsequent molecular events are not.