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PubMed2006

Optimal decoding of correlated neural population responses in the primate visual cortex.

Even the simplest environmental stimuli elicit responses in large populations of neurons in early sensory cortical areas. How these distributed responses are read out by subsequent processing stages to mediate behavior remains unknown. Here we used voltage-sensitive dye imaging to measure directly population responses in the primary visual cortex (V1) of monkeys performing a demanding visual detection task. We then evaluated the ability of different decoding rules to detect the target from the measured neural responses. We found that small visual targets elicit widespread responses in V1, and that response variability at distant sites is highly correlated. These correlations render most previously proposed decoding rules inefficient relative to one that uses spatially antagonistic center-surround summation. This optimal decoder consistently outperformed the monkey in the detection task, demonstrating the sensitivity of our techniques. Overall, our results suggest an unexpected role for inhibitory mechanisms in efficient decoding of neural population responses.

Algorithms↗
PubMed1992

Fast and slow components of unitary EPSCs on stellate cells elicited by focal stimulation in slices of rat visual cortex.

1. Voltage and current recordings were made from visually identified non-pyramidal neurones in slices of layer IV of rat primary visual cortex using the whole-cell configuration of the patch clamp technique. These neurones are characterized by a high input resistance (0.5-2 G omega) and a non-adaptive behaviour of action potential frequency following depolarizing current injection, which suggests that they are stellate cells. 2. Excitatory postsynaptic currents (EPSCs) were recorded from these neurones during focal stimulation of neighbouring cells by a second patch pipette, the tip of which was placed on the soma of the stimulated cell. The response amplitude as a function of stimulus strength showed a sharp increase at a critical stimulus strength suggesting that stimulus-evoked currents represent unitary EPSCs. 3. In most cases the latencies of stimulus-evoked EPSCs were unimodally distributed with means in the range of 2.1-3.6 ms. In some experiments two peaks were seen in the distribution of latencies. The EPSC rise times, measured as the time from 20 to 80% peak amplitude, fell into a distribution ranging from 0.1 to 0.8 ms with a peak at 0.2 ms. The EPSC decay time course at -70 mV membrane potential was fitted by a single exponential with a time constant of 2.39 +/- 0.99 ms (mean +/- S.D.). The rise and decay times were independent of EPSC peak amplitudes. 4. The peak amplitude of successive unitary EPSCs, elicited by a constant stimulus, fluctuated at random. At a holding potential of -70 mV the peak amplitudes varied between 5 and 90 pA. In two out of ten cells the histogram of peak amplitudes could be well fitted by the sum of several equidistant Gaussians with a peak distance of around 10 pA. This suggests that the quantal conductance change underlying the peak current fluctuations is of the order of 100 pS. 5. At membrane potentials more positive than -70 mV the decay of stimulus-evoked EPSCs showed two components with very different time courses. In standard extracellular solution the current-voltage (I-V) relation for the fast component was almost linear whereas the slow component showed a J-shaped I-V relation with a region of negative slope conductance between -30 and -70 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Callosal projections in the visual cortex and the vertical meridian of the visual field in the albino rat.

Studies using electrophysiological and HRP-labeling techniques showed that the lateral border of physiologically determined primary visual cortex coincides with the cytoarchiectonically defined area 17/18a border. The dense callosal projections are distributed in a zone, about 1.5 mm wide, along this border, which lies in the callosal zone, about 1/4-1/3 of the zone width from its lateral limit. There are two representations of the vertical meridian of the visual field, one in the proper of area 17, about 1/3 of the zone width from its medial limit, the other in area 18a, at about the lateral zone limit.

Animals↗
PubMed2006

Changes in visual responses in the feline dLGN: selective thalamic suppression induced by transcranial magnetic stimulation of V1.

Transcranial magnetic stimulation (TMS) of the cortex can modify activity noninvasively and produce either excitatory or inhibitory effects, depending on stimulus parameters. Here we demonstrate controlled inhibitory effects on the large corticogeniculate feedback pathway from primary visual cortex to cells of the dorsal lateral geniculate nucleus (dLGN) that are focal and reversible-induced by either single pulses or trains of pulses of TMS. These effects selectively suppress the sustained component of responses to flashed spots or moving grating stimuli and are the result of loss of spikes fired in tonic mode, whereas the number of spikes fired in bursts remain the same. We conclude that acute inactivation of the corticogeniculate downflow selectively affects the tonic mode. We found no evidence to suggest that cortical inactivation increased burst frequency.

Action Potentials↗
PubMed1998

Expression of alpha3, beta3 and gamma1 GABA(A) receptor subunit messenger RNAs in visual cortex and lateral geniculate nucleus of normal and monocularly deprived monkeys.

Complementary RNA probes derived from complementary DNA specifically subcloned from monkey tissue were used to localize, by in situ hybridization histochemistry, the relatively rare alpha3, beta3 and gamma1 subunit transcripts of the GABA(A) receptor in visual cortex and lateral geniculate nucleus of normal monkeys and in monkeys that had been deprived of vision in one eye. Overall, levels of alpha3, beta3 and gamma1 subunit transcripts were very low. In the primary visual cortex (area 17) they were concentrated in layers II and VI and in a stratum of white matter subjacent to layer VI. The localization and density of the three messenger RNAs closely resembled those of other rare (alpha2, alpha5 and beta1) transcripts but their distribution also overlapped that of the predominant alpha1, beta2 and gamma2 subunit transcripts. In area 18, alpha3 and beta3 transcript distribution resembled that in area 17, with the addition of a third band of hybridization in layer IV for beta3. Gamma1 subunit transcript localization in area 18 differed significantly from that in area 17, with increased expression restricted to layer IV. In the dorsal lateral geniculate nucleus, beta3 and gamma1 transcripts were expressed at low levels across all layers while alpha3 transcripts were restricted to the magnocellular layers. Following 15 and 18 day periods of monocular deprivation, induced by intravitreal injections of tetrodotoxin, levels of alpha3 receptor subunit transcripts showed modest reductions in layer VI of area 17 and in deprived geniculate laminae of adult animals. Reductions in alpha3 transcript levels were much more pronounced in layer IVCbeta of a five-month-old monkey deprived for the same time. Levels of beta3 and gamma1 transcripts were unaffected by monocular deprivation in cortex and geniculate at any age. Taken together with studies of other GABA(A) receptor transcripts, these results demonstrate the heterogeneity of GABA(A) receptor messenger RNA expression in the monkey geniculo-striate pathway and the varied response to reduced neuronal activity.

Animals↗
PubMed2006

The impact of a corticotectal impulse on the awake superior colliculus.

Corticotectal (CTect) neurons of layer 5 are large and prominent elements of mammalian visual cortex, with thick apical dendrites that ascend to layer 1, "intrinsically bursting" membrane properties, and fast-conducting descending axons that terminate in multiple subcortical domains. These neurons comprise a major output pathway of primary visual cortex, but virtually nothing is known about the synaptic influence of single CTect impulses on the superior colliculus (SC). Here, we examine the distribution of monosynaptic currents generated in the superficial SC by spontaneous impulses of single CTect neurons. We do this by recording the spikes of CTect neurons and the field potentials that they generate through the depths of the SC. Methods of spike-triggered averaging and current source density analysis are then applied to these data. We show, in fully awake rabbits, that single CTect impulses generate potent, fast-rising monosynaptic currents in the SC similar to those generated in sensory cortex by specific thalamic afferents. These currents are focal in depth, precisely retinotopic, and highly dependent on the conduction velocity of the CTect axon. Moreover, we show that CTect synapses, like thalamocortical synapses, suffer a chronic state of depression in awake subjects that is modulated by preceding interspike interval. However, CTect neurons generated few "bursts," and postsynaptic responses in the SC were not significantly influenced by a shift from alert to an inattentive state (indicated by hippocampal EEG). Together, our results suggest that single CTect neurons may resemble thalamocortical neurons in their ability to serve as potent "drivers" of postsynaptic targets.

Animals↗
PubMed1990

Cell surface molecules containing N-acetylgalactosamine are associated with basket cells and neurogliaform cells in cat visual cortex.

In the cerebral cortex, the plant lectin Vicia villosa (VVA) selectively stains the surfaces of nonpyramidal neurons. This lectin binds specifically to alpha- and beta-linked N-acetylgalactosamine (GalNac). VVA-reactive carbohydrate is highly concentrated in layer 4 of the primary visual cortex of the cat, where it is associated exclusively with GABAergic local circuit neurons. We have studied this neuronal subset with intracellular electrophysiological recording and dye marking to identify the particular cell types expressing surface GalNac. Five different types of local circuit neurons were stained intracellularly (N = 45), but only 2 types, the columnar basket and large neurogliaform cells, were also labeled by the lectin (N = 19/45). Lectin negative types included small basket, chandelier, and large bitufted cells (26/45). Spiny stellate and pyramidal neurons were also lectin negative. Electrophysiological recordings revealed differences in the duration of action potentials in smooth versus spiny stellates but no differences between lectin-positive or -negative types. A biochemical analysis of cortical glycoproteins by SDS-PAGE and lectin blotting revealed multiple bands containing GalNac enriched in membrane fractions. These carbohydrate-containing molecules may be part of a biochemical mechanism for linking together cells with common functional properties.

Acetylgalactosamine↗
PubMed1996

Microcircuitry of forward and feedback connections within rat visual cortex.

Visual cortex in mammals is composed of many distinct areas that are linked by reciprocal connections to form a multilevel hierarchy. Ascending information is sent via forward connections from lower to higher areas and is thought to contribute to the emergence of increasingly complex receptive field properties at higher levels. Descending signals are transmitted via feedback connections from higher to lower areas and are believed to provide information about the context in which a stimulus appears, to contribute to modulation of visual responses by attention, and to play a role in memory processes. To determine whether forward and feedback pathways in rat visual cortex constitute distinct intracortical circuits, we have studied the distribution of reciprocal corticocortical inputs to pyramidal cells and gamma-aminobutyric acid (GABA)ergic interneurons. For this purpose, we chose forward and feedback connections between primary visual cortex and the secondary extrastriate lateromedial (LM) area as a model system. Pathways were traced with the axonal marker phaseolus vulgaris-leucoagglutinin. Labeled terminals were identified in the electron microscope, and GABA immunocytochemistry was used to identify the postsynaptic dendritic shafts of GABAergic interneurons. In both pathways, inputs to pyramidal cells were directed preferentially to dendritic spines and not to shafts. In the forward pathway, 90% of labeled inputs were distributed to pyramidal cells and 10% to interneurons. This proportion was similar to that of nearby unlabeled connections in the neuropil, indicating that forward connections are not selective for pyramidal cells or interneurons. In sharp contrast, feedback connections were significantly different from the unlabeled connections and supplied almost exclusively pyramidal cells (98%). Feedback inputs to GABAergic neurons were five times weaker (2%) relative to the forward direction. These structural differences suggest that disynaptic GABAergic inhibition is much stronger in forward than in feedback pathways. Recent physiological experiments have confirmed this prediction (Shao et al. [1995] Soc. Neurosci. Abstr., 21:1274) and we, therefore, conclude that relatively small anatomical differences in the microcircuitry can have important functional consequences. It remains an open question whether generally reciprocal interareal circuits at all levels of the cortical hierarchy are organized in similar fashion.

Animals↗
PubMed1998

Effects of tetrodotoxin treatment in LGN on neuromodulatory receptor expression in developing visual cortex.

The expression and distribution patterns of transmitter receptors change dramatically during pre- and post-natal development of the visual cortex, but the factors that control these processes are largely unknown. We have tested the hypothesis that input activity from the lateral geniculate nucleus (LGN), one major input source to visual cortex, may contribute to the processes underlying transmitter receptor redistributions in the visual cortex during development. We found that a short period of tetrodotoxin (TTX) treatment in LGN retarded the developmental expression and age-dependent reorganization of neuromodulatory receptors, including muscarinic, serotonergic and adrenergic receptors, in kitten primary visual cortex. The visual cortices ipsilateral to the TTX infusion site displayed a 'younger' receptor pattern than that of their contralateral control counterparts in the same animals. The results suggest that active input from LGN regulates the expression profile of a broad range of receptors in the developing visual cortex.

Animals↗
PubMed1980

Inhibitory interactions contributing to the ocular dominance of monocularly dominated cells in the normal cat striate cortex.

Experiments have been carried out to ascertain whether intracortical inhibitory processes influence the ocular dominance of monocularly dominated cells in the primary visual cortex of the normal cat. The GABA antagonist bicuculline has been iontophoretically applied to the cells studied to produce a localised block of inhibitory mechanisms acting on them. The ocular dominance of these cells was tested before, during, and after bicuculline application. In a sample of 42 cells studied, approximately 50% (19) showed a significant change in ocular dominance during bicuculline application. Some exclusively monocular cells became equally driven by either eye during bicuculline application. All the effects were reversible. Receptive field properties revealed in the non-dominant eye were not identical to those in the dominant eye. Evidence is presented to suggest that for some of the cells there is a selective GABA-mediated inhibitory process suppressing the non-dominant eye input. The possible implications of these data are discussed.

Animals↗
PubMed1997

Different effects of cholinergic agents on responses recorded from the cat visual cortex and lateral geniculate nucleus dorsalis.

We investigated the effect of cholinergic agents on the cat visual evoked potentials (VEPs) recorded from the primary visual cortex (V1) and lateral geniculate nucleus dorsalis (LGNd) to determine on which level of the visual pathway the cholinergic system acts. VEPs to the alternation of 0.1 cycles per degree sinusoidal gratings at 1 and 4 Hz were recorded from N2O-anesthetized cats directly from the surface of V1 and LGNd. The depth of recording in LGNd was determined by the site where the maximal response was obtained by 1 Hz stimulation. VEPs to 4 Hz stimulation, which showed sinusoidal waveforms and were analyzed by fast Fourier transforms, were used as indicators for modulation by cholinergic agents. Physostigmine, an acetylcholinesterase inhibitor, 0.7 mg/kg i.v., suppressed the amplitude of the responses more at V1 (suppression ratio: mean +/- SD, 85.4 +/- 9.3%) than at LGNd (32.4 +/- 30.7%) (P < 0.05). Conversely, scopolamine, a muscarinic receptor blocker, 0.7 mg/kg i.v., increased the amplitude of the responses more at V1 (enhancement ratio: mean +/- SD, 60.3 +/- 22.3%) than at LGNd (-22.2 +/- 22.5%) (P < 0.05). These results indicate that the V1 changes reflect a direct cortical cholinergic effect, probably by modulating the cholinergic projection from the nucleus basalis of Meynert to V1.

Animals↗
PubMed2005

LFP power spectra in V1 cortex: the graded effect of stimulus contrast.

We recorded local field potentials (LFPs) and single-unit activity simultaneously in the macaque primary visual cortex (V1) and studied their responses to drifting sinusoidal gratings that were chosen to be "optimal" for the single units. Over all stimulus conditions, the LFP spectra have much greater power in the low-frequency band (< or = 10 Hz) than higher frequencies and can be described as "1/f." Analysis of the total power limited to the low, gamma (25-90 Hz), or broad (8-240 Hz) frequency bands of the LFP as a function of stimulus contrast indicates that the LFP power gradually increases with stimulus strength across a wide band in a manner roughly comparable to the increase in the simultaneously recorded spike activity. However, the low-frequency band power remains approximately constant across all stimulus contrasts. More specifically the gamma-band LFP power increases differentially more with respect to baseline than either higher or lower bands as stimulus contrast increases. At the highest stimulus contrasts, we report as others have previously, that the power spectrum of the LFP typically contains an obvious peak in the gamma-frequency band. The gamma-band peak emerges from the overall broadband enhancement in LFP power at stimulus contrasts where most single units' responses have begun to saturate. The temporal/spectral structures of the LFP located in the gamma band-which become most evident at the highest contrasts-provide additional constraints on potential mechanisms underlying the stimulus response properties of spiking neurons in V1.

Action Potentials↗
PubMed2004

Halothane augments event-related gamma oscillations in rat visual cortex.

Cortical gamma oscillations have been associated with neural processes supporting cognition and the state of consciousness but the effect of general anesthesia on gamma oscillations is controversial. Here we studied the concentration-dependent effect of halothane on gamma (20-60 Hz) power of event-related potentials (ERP) in rat primary visual cortex. ERP to light flashes repeated at 5-s intervals was recorded with chronically implanted, bipolar, intracortical electrodes at selected steady-state halothane concentrations between 0 and 2%. gamma-Band power was calculated for 0-1000, 0-300 and 300-1000 ms poststimulus periods and corresponding prestimulus (PS) periods. Multitaper power spectral analysis was used to estimate gamma power from both single-trial and average ERP in order to differentiate between phase-locked (evoked) and non-phase-locked (induced) gamma activities. Significant PS gamma power was present at all halothane concentrations. Flash elicited an increase in gamma power that lasted up to 1 s poststimulus at all halothane concentrations. Halothane at intermediate concentrations (0.5-1.2%) augmented both PS and ERP gamma power two to four times relative to the waking baseline. gamma Power was not different between waking and deeply anesthetized (2%) levels. gamma Power reached maximum, as predicted by a Gaussian fit of power-concentration data, at halothane concentration (0.86%) similar to the concentration (0.73%) that abolished the righting reflex, a behavioral index of loss of consciousness. Evoked, i.e. stimulus-locked, gamma power was present during the first 300 ms poststimulus but not later, and was approximately 50% of single-trial ERP gamma power. Single-trial gamma power was present also at 300-1000 ms poststimulus, reflecting ERP not phase-locked to the stimulus. In summary, these observations suggest that (1) gamma activity is present in states ranging from waking to deep halothane anesthesia, (2) halothane does not prevent the transfer of visual input to striate cortex even at surgical plane of anesthesia, and (3) anesthetic-induced loss of consciousness, as reflected by the loss of righting reflex, is not correlated with a reduction in gamma power. Variance with other studies may be due to an underestimation of gamma power by ERP signal averaging as compared with single-trial analysis.

Animals↗
PubMed2003

Enhanced interictal responsiveness of the migraineous visual cortex to incongruent bar stimulation: a functional MRI visual activation study.

Since visual aura is usually described as expanding zigzag lines, neurones involved with the perception of line orientation may initiate this phenomenon. A visual incongruent line stimulation protocol was developed to obtain functional magnetic resonance images (fMRI) interictally in 5 female migraine patients with typical fortification spectra and in 5 normal matched controls. Activation in the visual cortex was present contralateral to the side of stimulation in 4 of 5 patients, notably in the extrastriate visual cortex. In 4 of 5 controls activation was observed in the medial and anterior orbitofrontal cortex. In one of them additional activation at the right nucleus accumbens/ventral striatum and right ventral pallidum was present. In the remaining control subject activation was present in the left primary visual cortex. The enhanced interictal reactivity of the visual cortex in migraineurs supports the hypothesis of abnormal cortical excitability as an important pathophysiological mechanism in migraine aura, though the role of specific regions of the visual cortex remains to be explored.

Adult↗
PubMed2002

Sensory information processing in neuroleptic-naive first-episode schizophrenic patients: a functional magnetic resonance imaging study.

BACKGROUND: Schizophrenic disorders are thought to involve widespread abnormalities in information processing. The present study used functional magnetic resonance imaging and a simple and robust paradigm that involved auditory and visual activation to examine basic sensory input circuits. Our aim was to determine which stages of the input processing network are disturbed in first-episode schizophrenic patients. METHODS: Twelve neuroleptic-naive inpatients (paranoid subtype) were compared with 11 healthy subjects by means of echo-planar functional magnetic resonance imaging. In a block design, the paradigm included the simultaneous presentation of a moving 6-Hz checkerboard and auditory stimuli in the form of drumbeats. The subjects were asked to simply look and listen. RESULTS: In comparison with control subjects, patients showed reduced activation in the right thalamus, the right prefrontal cortex, and the parietal lobe (restricted to the dorsal visual pathway) bilaterally. There were no notable differences in the primary visual cortex or the object-specific occipitotemporal pathway. In addition, patients presented with a reduced signal change to auditory stimulation in the left acoustic cortex. CONCLUSIONS: The present study supports the concept of widespread cortical and subcortical deficits in schizophrenia. Our findings suggest abnormal functioning early in the information processing and in high-order association cortices already at illness onset, before the administration of medication or the most confounding effects of illness duration. The main regions have been implicated in visual motion perception and discrimination as well as in attention to sensorial events and perceptual synthesis.

Acoustic Stimulation↗
PubMed1985

Corticopontine projection in the macaque: the distribution of labelled cortical cells after large injections of horseradish peroxidase in the pontine nuclei.

We studied the distribution of corticopontine cells in the monkey cerebral cortex. Horseradish peroxidase (HRP) was injected into the brainstem of monkeys in an attempt to fill the pontine nuclei on one or both sides. In control animals we injected the medullary pyramids or varied the route, size, or location of pontine injections. All retrograde filled corticopontine neurons were layer V pyramidal cells. Corticopontine cells were distributed within a largely continuous area of cortex which extended from the cingulate cortex medially to the sylvian fissure laterally; from the superior temporal fissure caudally to the medial part of the frontal granular cortex rostrally. Areas 4 and 6 of Brodmann (1905) contained the highest density of filled cells. In the primary visual cortex, area 17, there were a few labelled cells restricted to the rostral portion of the upper bank of the calcarine fissure, in a region representing the lower periphery of the visual field. The results are discussed in relation to the possible functions of the corticopontine system, especially the role of the extrastriate visual areas in visually guided movement.

Animals↗
PubMed2025

Combined somatic mutation and transcriptome analysis reveals region-specific differences in clonal architecture in human cortex.

The human cerebral cortex is specialized into regions, but little is known about how human cellular lineages shape cortical regional variation and neuronal cell-type distribution during development. Here, we map single-cell lineages of human cortical regions and neuronal subtypes using >1,000 somatic single-nucleotide variants (sSNVs) identified from deep bulk whole-genome sequencing and analyzed over 25 regions and >72,000 single cells. In the fronto-parietal cortex, sSNVs are rarely restricted, marking neuron-generating clones that disperse into neighboring regions. In contrast, the primary visual cortex harbors 30%-70% more sSNVs than the neighboring secondary visual cortex. Clones at this border exhibit more restricted dispersion, suggesting late developmental lineage segregation. Single-nucleus sSNV and whole-transcriptome analysis reveal glutamatergic neuron clones with modest regional restrictions that share low-mosaic sSNVs with some GABAergic neurons, suggesting a recent dorsal cortical progenitor. Our analysis reveals human-specific cortical lineage patterns, regional differences in clonal patterns, and late divergence of some glutamatergic/GABAergic lineages.

Humans↗
PubMed2005

Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex.

Neurons in the cerebral cortex are organized into anatomical columns, with ensembles of cells arranged from the surface to the white matter. Within a column, neurons often share functional properties, such as selectivity for stimulus orientation; columns with distinct properties, such as different preferred orientations, tile the cortical surface in orderly patterns. This functional architecture was discovered with the relatively sparse sampling of microelectrode recordings. Optical imaging of membrane voltage or metabolic activity elucidated the overall geometry of functional maps, but is averaged over many cells (resolution >100 microm). Consequently, the purity of functional domains and the precision of the borders between them could not be resolved. Here, we labelled thousands of neurons of the visual cortex with a calcium-sensitive indicator in vivo. We then imaged the activity of neuronal populations at single-cell resolution with two-photon microscopy up to a depth of 400 microm. In rat primary visual cortex, neurons had robust orientation selectivity but there was no discernible local structure; neighbouring neurons often responded to different orientations. In area 18 of cat visual cortex, functional maps were organized at a fine scale. Neurons with opposite preferences for stimulus direction were segregated with extraordinary spatial precision in three dimensions, with columnar borders one to two cells wide. These results indicate that cortical maps can be built with single-cell precision.

Analysis of Variance↗