Modified sensory processing in the barrel cortex of the adult mouse after chronic whisker stimulation

Chronic stimulation of a mystacial whisker follicle for 24 h induces structural and functional changes in layer IV of the corresponding barrel, with an insertion of new inhibitory synapses on spines and a depression of neuronal responses to the stimulated whisker. Under urethane anesthesia, we analyzed how sensory responses of single units are affected in layer IV and layers II & III of the stimulated barrel column as well as in adjacent columns. In the stimulated column, spatiotemporal characteristics of the activation evoked by the stimulated whisker are not altered, although spontaneous activity and response magnitude to the stimulated whisker are decreased. The sensitivity of neurons for the deflection of this whisker is not altered but the dynamic range of the response is reduced as tested by varying the amplitude and repetition rate of the deflection. Responses to deflection of nonstimulated whiskers remain unaltered with the exception of in-row whisker responses that are depressed in the column corresponding to the stimulated whisker. In adjacent nonstimulated columns, neuronal activity remains unaltered except for a diminished response of units in layer II/III to deflection of the stimulated whisker. From these results we propose that an increased inhibition within the stimulated barrel reduced the magnitude of its excitatory output and accordingly the flow of excitation toward layers II & III and the subsequent spread into adjacent columns. In addition, the period of uncorrelated activity between pathways from the stimulated and nonstimulated whiskers weakens synaptic inputs from in-row whiskers in the stimulated barrel column.     

Mechanisms underlying cross-orientation suppression in cat visual cortex

In simple cells of the cat primary visual cortex, null-oriented stimuli, which by themselves evoke no response, can completely suppress the spiking response to optimally oriented stimuli. This cross-orientation suppression has been interpreted as evidence for cross-orientation inhibition: synaptic inhibition among cortical cells with different preferred orientations. In intracellular recordings from simple cells, however, we found that cross-oriented stimuli suppressed, rather than enhanced, synaptic inhibition and, at the same time, suppressed synaptic excitation. Much of the suppression of excitation could be accounted for by the behavior of geniculate relay cells: contrast saturation and rectification in relay cell responses, when applied to a linear feed-forward model, predicted cross-orientation suppression of the modulation (F1) component of excitation evoked in simple cells. In addition, we found that the suppression of the spike output of simple cells was almost twice the suppression of their synaptic inputs. Thus, cross-orientation suppression, like orientation selectivity, is strongly amplified by threshold.     

Similarity of direction tuning among responses to stimulation of different whiskers in neurons of rat barrel cortex

Cells in the rat barrel cortex exhibit stimulus-specific response properties. To understand the network mechanism of direction selectivity in response to facial whisker deflection, we examined direction selectivity of neuronal responses to single- and multi-whisker stimulations. In the case of regular-spiking units, i.e., putative excitatory cells, direction preferences were quite similar between responses to single-whisker stimulation of the principal and adjacent whiskers. In multi-whisker stimulation at short (< or = 5 ms) interstimulus intervals (ISIs), response facilitation was evoked only when the whiskers were deflected to the preferred direction of the response to the single whisker stimulation. These results suggest that there are neuronal networks among cells with different whisker preferences but with a common direction preference that could be the neuronal basis of the direction-selective facilitation of the response to multi-whisker stimulation. In contrast, multi-whisker stimulation at long (> or = 6 ms) ISIs caused non-direction-selective suppression of the response to the second stimulus. In the case of fast-spiking units, i.e., putative inhibitory cells, poor direction selectivity was exhibited. Thus stimulus direction is represented as the direction-selective responses to the single- and multi-whisker stimulations of putative excitatory cells rather than those of putative inhibitory cells.     

Time-dependent, layer-specific modulation of sensory responses mediated by neocortical layer 1

An essential component of feedback and top-down information in the cortical column arrives at layer 1 (L1) where it contacts distal dendrites of pyramidal neurons. Although much is known about the anatomical organization of L1 fibers, their contribution to sensory information processing remains to be determined. We assessed the physiological significance of L1 inputs by performing extracellular recordings in vivo from neurons in the primary somatosensory cortex of rodents. We found that blocking activity in L1 increases whisker-evoked response magnitude and variance, suggesting that L1 exerts an inhibitory influence on whisker responses. However, when pairing L1 stimulation with whisker deflection, the interval between the stimuli determined the outcome of the interaction, with facilitation of sensory responses dominating the short intervals (10 ms). These temporal interactions resulted in a time-dependent regulation of direction tuning of cortical neurons. The synaptic mechanisms underlying L1 inputs' influences were examined using whole cell recordings in vitro while pairing L1 and white-matter stimulations. We found time-dependent, layer-specific differences in synaptic summation of the two inputs, with supralinearity at shorter intervals and sublinearity at longer intervals that resulted mainly from shunting inhibition. Taken together, our results demonstrate that L1 inputs impose a time- and layer-specific regulation on sensory-evoked responses. This in turn may lead to a dynamic transmission of sensory information in the somatosensory cortex.     

Integration of synaptic responses to neighboring whiskers in rat barrel cortex in vivo

Characterizing input integration at the single-cell level is a critical step to understanding cortical function, particularly when sensory stimuli are represented over wide cortical areas and single cells exhibit large receptive fields. To study synaptic integration of sensory inputs, we made intracellular recordings from the barrel cortex of anesthetized rats in vivo. For each cell, we deflected the principal whisker (PW) either alone or preceded by the deflection of a single adjacent whisker (AW) at an interval of 20 or 3 ms. At the 20-ms interval in all cases, prior AW deflection significantly suppressed the PW-evoked spike output and caused the underlying synaptic response to reach a peak Vm less depolarized than that arising from PW deflection alone. The decrease in peak Vm was not attributed to hyperpolarizing inhibition but to a divisive reduction in PW-evoked PSP amplitude. The reduction in amplitude was not a result of shunting inhibition but was mostly a result of removal of the synaptic drive, or disfacilitation. When the AW-PW interval was shortened to 3 ms, spike suppression was observed in a subset of the cells studied. In most cases, a divisive reduction in synaptic response amplitude was offset by summation with the preceding AW-evoked depolarization. To determine whether suppression is a general feature of synaptic integration by barrel cortex neurons, we also characterized the interaction of responses evoked by local electrical stimulation. In contrast to the whisker data, we found that responses to paired stimulation at the same intervals produced more spikes and reached a peak Vm more depolarized than the individual responses alone, suggesting that whisker-evoked suppression is not a result of postsynaptic mechanisms. Instead, we propose that cross-whisker response suppression depends on sensory-specific mechanisms at cortical and subcortical levels.     

Direction tuning of inhibitory inputs to the turtle accessory optic system.

Neurons in turtle accessory optic system (basal optic nucleus, BON) were studied to compare excitatory and inhibitory visual inputs. Using a reduced in vitro brain stem preparation with the eyes attached, previous studies only showed a monosynaptic retinal input to the BON from direction-sensitive retinal ganglion cells that share a common preferred direction. Now using an intact brain stem preparation, not only did BON neurons display inhibitory postsynaptic potentials [IPSP(C)s] spontaneously, but IPSP(C)s were also evoked by visual pattern motion, they had their polarity reversed near the chloride equilibrium potential and they were blocked by the GABA(A) antagonist bicuculline. Because excitatory postsynaptic currents had reversal potentials >0 mV, BON cells were recorded using patch electrodes filled with QX-314 or Cs+ to measure the cell's direction tuning also at that higher reversal potential. For most of the BON neurons studied, their visual excitation and inhibition had a very similar preferred direction, indicating that both synaptic inputs were maximally active onto the same cell under the same stimulus conditions. These competing inputs may result from connections between the pretectum and accessory optic nuclei. Such synaptic interactions may serve a functional role in the visual processing necessary to create retinal slip signals for oculomotor control.     

Integration of evoked responses in supragranular cortex studied with optical recordings in vivo

Complex representations in sensory cortices rely on the integration of inputs that overlap temporally and spatially, particularly in supragranular layers, yet the spatiotemporal dynamics of this synaptic integration are largely unknown. The rodent somatosensory system offers an excellent opportunity to study these dynamics because of the overlapping functional representations of single-whisker inputs. We recorded responses in mouse primary somatosensory (barrel) cortex to single and paired whisker deflections using high-speed voltage-sensitive dye imaging. Responses to paired deflections at intervals of 0 and 10 ms summed sublinearly, producing a single transient smaller in amplitude than the sum of the component responses. At longer intervals of 50 and 100 ms, the response to the second deflection was reduced in amplitude and limited spatially relative to control. Between 100 and 200 ms, the response to the second deflection recovered and often showed areas of facilitation. With increasing interstimulus interval from 50 to 200 ms, recovery of the second response occurred from the second stimulated whisker's barrel column outward. In contrast to results with paired-whisker stimulation, when a whisker deflection was preceded by a weak electrical stimulus applied to the neighboring cortex, the summation of evoked responses was predominantly linear at all intervals tested. Thus under our conditions, the linearity of response summation in cortex was not predicted by the amplitudes of the component responses on a column-by-column basis, but rather by the timing and nature of the inputs.     

Electrical stimulation of locus coeruleus strengthens the surround inhibition in layer V barrel cortex in rat

It is believed that locus coeruleus (LC) influences the sensory information processing. However, its role in cortical surround inhibitory mechanism is not well established. In this experiment, using controlled mechanical displacement of whiskers; we investigated the effect of electrical stimulation of LC on response of layer V barrel cortical neurons in anesthetized rat. LC was stimulated 0, 50, 100, 200 and 400 ms before principal or adjacent whiskers deflection. For assessing the effect of LC stimulation on inhibitory receptive filed of barrel neurons, adjacent whisker was also deflected 20 ms before principal whisker deflection, and LC stimulation was applied 0-400 ms before principal whisker displacement. We found that LC stimulation increase the response magnitude of layer V neurons to principal whisker deflection (significant in 50-400 ms intervals). This increase was also observed in response to adjacent whisker deflection (significant in 100 ms interval). The response latency of neurons was decreased when LC was stimulated 400 ms before principal whisker deflection but LC stimulation did not affect the neuronal response latency to adjacent whisker displacement. Inhibitory effect of adjacent whisker deflection on neuronal response magnitude was increased by LC stimulation, tested in combined whisker displacement. These findings suggest that LC, by modulating the neuronal responses, enhances the neuronal responsiveness to sensory stimuli and increases their surround inhibition in cortex.     

Processing of vibrissa sensory information within the rat neocortex

Neuronal response properties were compared among different layers of the urethan-anesthetized rat vibrissa cortex. Measurements were made of the receptive-field (RF) size, the degree of directional selectivity, the latency of driving, the velocity threshold, and the tuning-curve slope. The RF size was defined by the number of whiskers that, when deflected individually, activated a neurons. For the center whisker of the RF (usually whisker C3), the response to deflection in the most preferred direction was compared with that in the opposite direction to classify the neuron as either strongly directional, weakly directional, or nondirectional. For the most preferred direction of the center whisker, the minimum velocity of deflection required to drive the unit was defined as the velocity threshold, the latency of driven response to a standard supramaximal velocity was measured, and finally, using exponential ramp-and-hold deflection, the threshold amplitude was determined at different values of time constant to construct a tuning-curve slope. Cortical layer IV neurons, as a whole, have the lowest threshold velocity. Layer Vb neurons stand on the opposite extreme in having the highest mean velocity threshold value. Although this difference is consistent with the generally held view that the "barrels" in layer IV represent the input stage of cortical information processing, the lack of laminar differences in latency and RF size support the idea that neurons of other cortical layers also receive direct thalamocortical inputs. The population of cortical neurons thus appears quite homogeneous across different layers as far as the results of examination with short-pulsed stimulation are concerned. Correlation of pairs of parameters (RF, directionality, velocity threshold, and latency) was tested in the two layers (layer IV and layer Vb). The latency and velocity threshold are highly correlated within both layers. Also, most of correlation coefficients of the corresponding pairs of the two layers are similar. However, the use of exponential ramp-and-hold deflection of whiskers revealed a difference in tuning-curve slope between layer IV and layer Vb (also layers II-III); layer IV neurons show flatter tuning-curve slopes (more oriented for detection of the amplitude component of whisker deflection) than neurons of layer Vb and layers II-III, which are more oriented for velocity detection. During the hold phase of whisker deflection, layer IV neurons tend to show sustained discharges, whereas layer Vb (also layers II-III) neurons mainly exhibit transient responses.(ABSTRACT TRUNCATED AT 400 WORDS)     

Inhibitory contributions to spatiotemporal receptive-field structure and direction selectivity in simple cells of cat area 17

Intracortical inhibition contributes to direction selectivity in primary visual cortex, but how it acts has been unclear. We investigated this problem in simple cells of cat area 17 by taking advantage of the link between spatiotemporal (S-T) receptive-field structure and direction selectivity. Most cells in layer 4 have S-T-oriented receptive fields in which gradients of response timing across the field confer a preferred direction of motion. Linear summation of responses across the receptive field, followed by a static nonlinear amplification, has been shown previously to account for directional tuning in layer 4. We tested the hypotheses that inhibition acts by altering S-T structure or the static nonlinearity or both. Drifting and counterphasing sine wave gratings were used to measure direction selectivity and S-T structure, respectively, in 17 layer 4 simple cells before and during iontophoresis of bicuculline methiodide (BMI), a GABAA antagonist. S-T orientation was quantified from fits to response temporal phase versus stimulus spatial phase data. Bicuculline reduced direction selectivity and S-T orientation in nearly all cells, and reductions in the two measures were well correlated (r = 0.81) and reversible. Using conventional linear predictions based on response phase and amplitude, we found that BMI-induced changes in S-T structure also accounted well for absolute changes in the amplitude and phase of responses to gratings drifting in the preferred and nonpreferred direction. For each cell we also calculated an exponent used to estimate the static nonlinearity. Bicuculline reduced the exponent in most cells, but the changes were not correlated with reductions in direction selectivity. We conclude that GABAA-mediated inhibition influences directional tuning in layer 4 primarily by sculpting S-T receptive-field structure. The source of the inhibition is likely to be other simple cells with certain spatiotemporal relationships to their target. Despite reductions in the two measures, most receptive fields maintained some directional tuning and S-T orientation during BMI. This suggests that their excitatory inputs, arising from the lateral geniculate nucleus and within area 17, are sufficient to create some S-T orientation and that inhibition accentuates it. Finally, BMI also reduced direction selectivity in 8 of 10 simple cells tested in layer 6, but the reductions were not accompanied by systematic changes in S-T structure. This reflects the fact that S-T orientation, as revealed by our first-order measures of the receptive field, is weak there normally. Inhibition likely affects layer 6 cells via more complex, nonlinear interactions.     

Directional selectivity and spatiotemporal structure of receptive fields of simple cells in cat striate cortex.

1. Simple cells in cat striate cortex were studied with a number of stimulation paradigms to explore the extent to which linear mechanisms determine direction selectivity. For each paradigm, our aim was to predict the selectivity for the direction of moving stimuli given only the responses to stationary stimuli. We have found that the prediction robustly determines the direction and magnitude of the preferred response but overestimates the nonpreferred response. 2. The main paradigm consisted of comparing the responses of simple cells to contrast reversal sinusoidal gratings with their responses to drifting gratings (of the same orientation, contrast, and spatial and temporal frequencies) in both directions of motion. Although it is known that simple cells display spatiotemporally inseparable responses to contrast reversal gratings, this spatiotemporal inseparability is demonstrated here to predict a certain amount of direction selectivity under the assumption that simple cells sum their inputs linearly. 3. The linear prediction of the directional index (DI), a quantitative measure of the degree of direction selectivity, was compared with the measured DI obtained from the responses to drifting gratings. The median value of the ratio of the two was 0.30, indicating that there is a significant nonlinear component to direction selectivity. 4. The absolute magnitudes of the responses to gratings moving in both directions of motion were compared with the linear predictions as well. Whereas the preferred direction response showed only a slight amount of facilitation compared with the linear prediction, there was a significant amount of nonlinear suppression in the nonpreferred direction. 5. Spatiotemporal inseparability was demonstrated also with stationary temporally modulated bars. The time course of response to these bars was different for different positions in the receptive field. The degree of spatiotemporal inseparability measured with sinusoidally modulated bars agreed quantitatively with that measured in experiments with stationary gratings. 6. A linear prediction of the responses to drifting luminance borders was compared with the actual responses. As with the grating experiments, the prediction was qualitatively accurate, giving the correct preferred direction but underestimating the magnitude of direction selectivity observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

GABA blockade unmasks an OFF response in ON direction selective ganglion cells in the mammalian retina

One unique subtype of retinal ganglion cell is the direction selective (DS) cell, which responds vigorously to stimulus movement in a preferred direction, but weakly to movement in the opposite or null direction. Here we show that the application of the GABA receptor blocker picrotoxin unmasks a robust excitatory OFF response in ON DS ganglion cells. Similar to the characteristic ON response of ON DS cells, the masked OFF response is also direction selective, but its preferred direction is opposite to that of the ON component. Given that the OFF response is unmasked with picrotoxin, its direction selectivity cannot be generated by a GABAergic mechanism. Alternatively, we find that the direction selectivity of the OFF response is blocked by cholinergic drugs, suggesting that acetylcholine release from presynaptic starburst amacrine cells is crucial for its generation. Finally, we find that the OFF response is abolished by application of a gap junction blocker, suggesting that it arises from electrical synapses between ON DS and polyaxonal amacrine cells. Our results suggest a novel role for gap junctions in mixing excitatory ON and OFF signals at the ganglion cell level. We propose that OFF inputs to ON DS cells are normally masked by a GABAergic inhibition, but are unmasked under certain stimulus conditions to mediate optokinetic signals in the brain.     

Direct inhibition evoked by whisker stimulation in somatic sensory (SI) barrel field cortex of the awake rat

Whisker deflection typically evokes a transient volley of action potentials in rat somatic sensory (SI) barrel cortex. Postexcitatory inhibition is thought to quickly terminate the cortical cell response to whisker deflection. Using dual electrode extracellular recording in awake rats, we describe an infrequent type of cell response in which stimulation of single hairs consistently blocks the ongoing discharge of neurons without prior excitation (I-only inhibition). Reconstruction of the recording sites indicates that I-only inhibition occurs most frequently when the recording site is clearly in the septum or at the barrel-septum junction. The same cells that respond with I-only inhibition to one whisker can show an excitatory discharge to other whiskers, usually followed by inhibition. Stimulation of either nose hairs or the large mystacial vibrissa can evoke I-only inhibition in SI cortex. I-only inhibition is most commonly observed at low stimulus frequencies ( approximately 1 Hz). At stimulus frequencies of >6 Hz, I-only inhibition typically converts to excitation. We conclude that single whisker low-frequency stimulation can selectively block the spontaneous discharge of neurons in SI barrel field septa. The observation that this cell response is found most often in or at the edge of septa and at relatively long latencies supports the idea that I-only inhibition is mediated through cortical circuits. We propose that in these cells inhibition alone or a combination of inhibition and disfacilitation play a role in suppressing neuronal discharge occasioned by low frequency contact of the whiskers with the environment.     

Frequency adaptation modulates spatial integration of sensory responses in the rat whisker system

The generation of perceptual experiences requires the integration of complex spatiotemporal patterns of sensory input. The rodent whisker system is a useful model for understanding the cellular mechanisms of sensory integration, which often include the operation of local circuits distributed throughout the brain. An example is cross-whisker suppression, where the neuronal response to whisker deflection is strongly reduced by preceding deflection of a neighboring whisker. Suppressive interactions between whisker-evoked responses have largely been studied using pairs of single whisker deflections. However, rats typically sweep their whiskers across surfaces at frequencies ranging from 5 to 25 Hz. Repetitive afferent activation induces frequency-dependent adaptation of neuronal responses and alters the synaptic dynamics of circuits that play a role in suppression, suggesting that adaptation could modulate the spatial integration of whisker evoked responses. We tested this hypothesis by comparing the cross-whisker suppression of principal whisker (PW)-evoked cortical and thalamic responses when preceded by either a single deflection of an adjacent whisker (AW) or a train of AW deflections at frequencies covering the normal whisking range. We found that periodic deflection of the preceding AW significantly reduced the magnitude of cross-whisker suppression. Surprisingly, although higher frequencies resulted in greater adaptation of the AW-evoked response, the effect on suppression was independent of frequency. We suggest that these results follow from known local circuit operations at multiple levels within the afferent path. Our findings support the view that repetitive whisking subserves a transformation of the integrative and functional properties of the whisker system.     

Circuit dynamics and coding strategies in rodent somatosensory cortex

Previous experimental studies of both cortical barrel and thalamic barreloid neuron responses in rodent somatosensory cortex have indicated an active role for barrel circuitry in processing thalamic signals. Previous modeling studies of the same system have suggested that a major function of the barrel circuit is to render the response magnitude of barrel neurons particularly sensitive to the temporal distribution of thalamic input. Specifically, thalamic inputs that are initially synchronous strongly engage recurrent excitatory connections in the barrel and generate a response that briefly withstands the strong damping effects of inhibitory circuitry. To test this experimentally, we recorded responses from 40 cortical barrel neurons and 63 thalamic barreloid neurons evoked by whisker deflections varying in velocity and amplitude. This stimulus evoked thalamic response profiles that varied in terms of both their magnitude and timing. The magnitude of the thalamic population response, measured as the average number of evoked spikes per stimulus, increased with both deflection velocity and amplitude. On the other hand, the degree of initial synchrony, measured from population peristimulus time histograms, was highly correlated with the velocity of whisker deflection, deflection amplitude having little or no effect on thalamic synchrony. Consistent with the predictions of the model, the cortical population response was determined largely by whisker velocity and was highly correlated with the degree of initial synchrony among thalamic neurons (R(2) = 0.91), as compared with the average number of evoked thalamic spikes (R(2) = 0.38). Individually, the response of nearly all cortical cells displayed a positive correlation with deflection velocity; this homogeneity is consistent with the dependence of the cortical response on local circuit interactions as proposed by the model. By contrast, the response of individual thalamic neurons varied widely. These findings validate the predictions of the modeling studies and, more importantly, demonstrate that the mechanism by which the cortex processes an afferent signal is inextricably linked with, and in fact determines, the saliency of neural codes embedded in the thalamic response.     

Response properties of whisker-associated trigeminothalamic neurons in rat nucleus principalis

Nucleus principalis (PrV) of the brain stem trigeminal complex mediates the processing and transfer of low-threshold mechanoreceptor input en route to the ventroposterior medial nucleus of the thalamus (VPM). In rats, this includes tactile information relayed from the large facial whiskers via primary afferent fibers originating in the trigeminal ganglion (NV). Here we describe the responses of antidromically identified VPM-projecting PrV neurons (n = 72) to controlled ramp-and-hold deflections of whiskers. For comparison, we also recorded the responses of 64 NV neurons under identical experimental and stimulus conditions. Both PrV and NV neurons responded transiently to stimulus onset (ON) and offset (OFF), and the majority of both populations also displayed sustained, or tonic, responses throughout the plateau phase of the stimulus (75% of NV cells and 93% of PrV cells). Average ON and OFF response magnitudes were similar between the two populations. In both NV and PrV, cells were highly sensitive to the direction of whisker deflection. Directional tuning was slightly but significantly greater in NV, suggesting that PrV neurons integrate inputs from NV cells differing in their preferred directions. Receptive fields of PrV neurons were typically dominated by a "principal" whisker (PW), whose evoked responses were on average threefold larger than those elicited by any given adjacent whisker (AW; n = 197). However, of the 65 PrV cells for which data from at least two AWs were obtained, most (89%) displayed statistically significant ON responses to deflections of one or more AWs. AW response latencies were 2.7 +/- 3.8 (SD) ms longer than those of their corresponding PWs, with an inner quartile latency difference of 1-4 ms (+/-25% of median). The range in latency differences suggests that some adjacent whisker responses arise within PrV itself, whereas others have a longer, multi-synaptic origin, possibly via the spinal trigeminal nucleus. Overall, our findings reveal that the stimulus features encoded by primary afferent neurons are reflected in the responses of VPM-projecting PrV neurons, and that significant convergence of information from multiple whiskers occurs at the first synaptic station in the whisker-to-barrel pathway.     

Functional inhibition in direction-selective retinal ganglion cells: spatiotemporal extent and intralaminar interactions

We recorded from ON-OFF direction-selective ganglion cells (DS cells) in the rabbit retina to investigate in detail the inhibition that contributes to direction selectivity in these cells. Using paired stimuli moving sequentially across the cells' receptive fields in the preferred direction, we directly confirmed the prediction of that a wave of inhibition accompanies any moving excitatory stimulus on its null side, at a fixed spatial offset. Varying the interstimulus distance, stimulus size, luminance, and speed yielded a spatiotemporal map of the strength of inhibition within this region. This "null" inhibition was maximal at an intermediate distance behind a moving stimulus: 1/2 to 11/2 times the width of the receptive field. The strength of inhibition depended more on the distance behind the stimulus than on stimulus speed, and the inhibition often lasted 1-2 s. These spatial and temporal parameters appear to account for the known spatial frequency and velocity tuning of ON-OFF DS cells to drifting contrast gratings. Stimuli that elicit distinct ON and OFF responses to leading and trailing edges revealed that an excitatory response of either polarity could inhibit a subsequent response of either polarity. For example, an OFF response inhibited either an ON or OFF response of a subsequent stimulus. This inhibition apparently is conferred by a neural element or network spanning the ON and OFF sublayers of the inner plexiform layer, such as a multistratified amacrine cell. Trials using a stationary flashing spot as a probe demonstrated that the total amount of inhibition conferred on the DS cell was equivalent for stimuli moving in either the null or preferred direction. Apparently the cell does not act as a classic "integrate and fire" neuron, summing all inputs at the soma. Rather, computation of stimulus direction likely involves interactions between excitatory and inhibitory inputs in local regions of the dendrites.     

Neurotransmitter inputs to directionally sensitive turtle retinal ganglion cells

Synaptic drugs were superfused into turtle eyecup preparation while recording extracellularly from directionally sensitive (DS) retinal ganglion cells. As in previous experiments in intact rabbit retina, both picrotoxin (a GABA antagonist) and physostigmine [an acetylcholine (ACh) potentiator] reduced or eliminated the directional selectivity of these cells. These drug effects occurred at micromolar concentrations and were long lasting. Superfusion of ACh caused excitation, and GABA caused inhibition of the spike activity of these DS cells. In some experiments, the ganglion cell was isolated from its presynaptic inputs by perfusing with a low-Ca2+/EGTA perfusate, which blocked synaptic transmission but did not suppress spike firing. During this synaptic block, ACh still caused spontaneous spike firing, and GABA was able to suppress the ACh-induced spike activity. Strychnine slightly increased the spontaneous activity of DS ganglion cells and reduced their response to light. Glycine and taurine were equally effective in totally suppressing spike activity, and strychnine blocked this inhibition by both agents. However, these inhibitory effects may be transynaptic because glycine did not suppress ACh-induced excitation during synaptic block. Superfusion of micromolar concentrations of methionine enkephalin and [D-Ala2]methionine enkephalinamide occasionally caused small increases in the light responses of DS cells, whereas naloxone, a broad-spectrum opiate antagonist, moderately decreased light responsiveness. Because naloxone had no effect on these cell's directional tuning, the opiate system is probably not involved in the mechanism of directional sensitivity. Based on the effects of these transmitter candidates and their antagonists, a possible site fo DS subunits may be the ACh and GABA receptors on the membrane of DS ganglion cells. ACh provides light-evoked excitation that may, when potentiated by physostigmine, overcome asymmetric GABA inhibition. Although the role of glycine in directional sensitivity is small, it may be responsible for regulating presynaptic excitatory pathways leading to the DS ganglion cells.     

FM velocity selectivity in the inferior colliculus is inherited from velocity-selective inputs and enhanced by spike threshold

Frequency modulation (FM) is computed from the temporal sequence of activated auditory nerve fibers representing different frequencies. Most studies in the inferior colliculus (IC) have inferred from extracellular recordings that the precise timing of nonselective inputs creates selectivity for FM direction and velocity (Andoni S, Li N, Pollak GD. J Neurosci 27: 4882-4893, 2007; Fuzessery ZM, Richardson MD, Coburn MS. J Neurophysiol 96: 1320-1336, 2006; Gordon M, O'Neill WE. Hear Res 122: 97-108, 1998). We recently reported that two additional mechanisms were more important than input timing for directional selectivity in some IC cells: spike threshold and inputs that were already selective (Gittelman JX, Li N, Pollak GD. J Neurosci 29: 13030-13041, 2009). Here, we show that these same mechanisms, selective inputs and spike threshold, underlie selectivity for FM velocity and intensity. From whole cell recordings in awake bats, we recorded spikes and postsynaptic potentials (PSPs) evoked by downward and upward FMs that swept identical frequencies at different velocities and intensities. To determine the synaptic mechanisms underlying PSP selectivity (relative PSP height), we derived sweep-evoked synaptic conductances. Changing FM velocity or intensity changed conductance timing and size. Modeling indicated that excitatory conductance size contributed more to PSP selectivity than conductance timing, indicating that the number of afferent spikes carried more FM information to the IC than precise spike timing. However, excitation alone produced mostly suprathreshold PSPs. Inhibition reduced absolute PSP heights, without necessarily altering PSP selectivity, thereby rendering some PSPs subthreshold. Spike threshold then sharpened selectivity in the spikes by rectifying the smaller PSPs. This indicates the importance of spike threshold, and that inhibition enhances selectivity via a different mechanism than previously proposed.     

Representation of moving wavefronts of whisker deflection in rat somatosensory cortex

Rats rhythmically sweep their whiskers over object features, generating sequential deflections of whisker arcs. Such moving wavefronts of whisker deflection are likely to be fundamental elements of natural somatosensory input. To determine how moving wavefronts are represented in somatosensory cortex (S1), we measured single- and multiunit neural responses in S1 of anesthetized rats to moving wavefronts applied through a piezoelectric whisker deflector array. Wavefronts consisted of sequential deflections of individual whisker arcs, which moved progressively across the whisker array. Starting position (starting arc), direction, and velocity of wavefronts were varied. Neurons responded strongly only when wavefront starting position included their principal whisker (PW). When wavefronts started at neighboring positions and swept through the PW, responses to the PW arc were suppressed by or=5 ms, was maximal at 20 ms, and recovered within 100-200 ms. Suppression of PW arc responses during wavefronts was largely independent of wavefront direction. However, layer 2/3 neurons showed direction selectivity for responses to the entire wavefront (the entire sequence of SW and PW arc deflection). Wavefront direction selectivity was correlated with receptive field somatotopy and reflected differential responses to the specific SWs that were deflected first in a wavefront. These results indicate that suppressive interwhisker interactions shape responses to wavefronts, resulting in increased salience of wavefront starting position, and, in some neurons, preference for wavefront direction.