Response Properties Of Neurons Research Articles

Neural processing in the primary auditory cortex following cholinergic lesions of the basal forebrain in ferrets

Cortical acetylcholine (ACh) release has been linked to various cognitive functions, including perceptual learning. We have previously shown that cortical cholinergic innervation is necessary for accurate sound localization in ferrets, as well as for their ability to adapt with training to altered spatial cues. To explore whether these behavioral deficits are associated with changes in the response properties of cortical neurons, we recorded neural activity in the primary auditory cortex (A1) of anesthetized ferrets in which cholinergic inputs had been reduced by making bilateral injections of the immunotoxin ME20.4-SAP in the nucleus basalis (NB) prior to training the animals. The pattern of spontaneous activity of A1 units recorded in the ferrets with cholinergic lesions (NB ACh–) was similar to that in controls, although the proportion of burst-type units was significantly lower. Depletion of ACh also resulted in more synchronous activity in A1. No changes in thresholds, frequency tuning or in the distribution of characteristic frequencies were found in these animals. When tested with normal acoustic inputs, the spatial sensitivity of A1 neurons in the NB ACh– ferrets and the distribution of their preferred interaural level differences also closely resembled those found in control animals, indicating that these properties had not been altered by sound localization training with one ear occluded. Simulating the animals’ previous experience with a virtual earplug in one ear reduced the contralateral preference of A1 units in both groups, but caused azimuth sensitivity to change in slightly different ways, which may reflect the modest adaptation observed in the NB ACh– group. These results show that while ACh is required for behavioral adaptation to altered spatial cues, it is not required for maintenance of the spectral and spatial response properties of A1 neurons.

Modulatory Effects on Laminar Neural Activity Induced by Near-Infrared Light Stimulation with a Continuous Waveform to the Mouse Inferior Colliculus In Vivo.

Infrared neural stimulation (INS) is a promising area of interest for the clinical application of a neuromodulation method. This is in part because of its low invasiveness, whereby INS modulates the activity of the neural tissue mainly through temperature changes. Additionally, INS may provide localized brain stimulation with less tissue damage. The inferior colliculus (IC) is a crucial auditory relay nucleus and a potential target for clinical application of INS to treat auditory diseases and develop artificial hearing devices. Here, using continuous INS with low to high-power density, we demonstrate the laminar modulation of neural activity in the mouse IC in the presence and absence of sound. We investigated stimulation parameters of INS to effectively modulate the neural activity in a facilitatory or inhibitory manner. A mathematical model of INS-driven brain tissue was first simulated, temperature distributions were numerically estimated, and stimulus parameters were selected from the simulation results. Subsequently, INS was administered to the IC of anesthetized mice, and the modulation effect on the neural activity was measured using an electrophysiological approach. We found that the modulatory effect of INS on the spontaneous neural activity was bidirectional between facilitatory and inhibitory effects. The modulatory effect on sound-evoked responses produced only an inhibitory effect to all examined stimulus intensities. Thus, this study provides important physiological evidence on the response properties of IC neurons to INS. Overall, INS can be used for the development of new therapies for neurological disorders and functional support devices for auditory central processing.

Plasticity of Response Properties of Mouse Visual Cortex Neurons Induced by Optogenetic Tetanization In Vivo.

Heterosynaptic plasticity, along with Hebbian homosynaptic plasticity, is an important mechanism ensuring the stable operation of learning neuronal networks. However, whether heterosynaptic plasticity occurs in the whole brain in vivo, and what role(s) in brain function in vivo it could play, remains unclear. Here, we used an optogenetics approach to apply a model of intracellular tetanization, which was established and employed to study heterosynaptic plasticity in brain slices, to study the plasticity of response properties of neurons in the mouse visual cortex in vivo. We show that optogenetically evoked high-frequency bursts of action potentials (optogenetic tetanization) in the principal neurons of the visual cortex induce long-term changes in the responses to visual stimuli. Optogenetic tetanization had distinct effects on responses to different stimuli, as follows: responses to optimal and orthogonal orientations decreased, responses to null direction did not change, and responses to oblique orientations increased. As a result, direction selectivity of the neurons decreased and orientation tuning became broader. Since optogenetic tetanization was a postsynaptic protocol, applied in the absence of sensory stimulation, and, thus, without association of presynaptic activity with bursts of action potentials, the observed changes were mediated by mechanisms of heterosynaptic plasticity. We conclude that heterosynaptic plasticity can be induced in vivo and propose that it may play important homeostatic roles in operation of neural networks by helping to prevent runaway dynamics of responses to visual stimuli and to keep the tuning of neuronal responses within the range optimized for the encoding of multiple features in population activity.

Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo

Neuronal mitochondria play important roles beyond ATP generation, including Ca2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly between the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Ca2+ and Camkk2-dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a signaling pathway underlying the subcellular compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise and activity-dependent regulation of mitochondria fission/fusion balance.

Global and local neuronal coding of tactile information in the barrel cortex.

During tactile sensation in rodents, the whisker movements across surfaces give rise to intricate whisker motions that encompass discrete and transient stick-slip events, effectively conveying valuable information regarding surface properties. These surface characteristics are transformed into cortical neuronal responses. This study examined the coding strategies underlying these transformations in rat whiskers. We found that changes in surface coarseness modified the number and magnitude of stick-slip events, which in turn both modulated properties of neuronal responses. Global changes in the number of stick-slip events primarily affected neuronal discharge rates and the degree of neuronal synchronization. In contrast, local changes in the magnitude of stick-slip events affected the transformation of these kinematic and kinetic characteristics into neuronal discharges. Most cortical neurons exhibited surface coarseness selectivity through global and local stick-slip event properties. However, this selectivity varied across coding strategies in the same neurons, given that each coding strategy reflected different aspects of changes in whisker-surface interactions. The degree of spatial similarity in surface coarseness preference in adjacently recorded neurons differed among these coding strategies. Adjacently recorded neurons exhibited the same surface coarseness preference in their firing rates but not through other coding strategies. Through these results, we were able to show that local stick-slip event properties contribute to texture discrimination, complementing and surpassing global coding in this context. These findings suggest that the representation of surface coarseness in the cortex may rely on concurrent coding strategies that integrate tactile information across different spatiotemporal scales.

Seeing stars: Astroglia modulate visual circuits during behavioral-state transitions

In this issue of Neuron, Uribe-Arias etal.1 show that, in larval zebrafish, astrocyte-like cells exhibit calcium responses to norepinephrine during behavioral-state transitions and alter neuronal response properties. Thus, astroglia can sculpt neuronal dynamics in behaviorally meaningful ways.

No Evidence for Cross-Modal fMRI Adaptation in Macaque Parieto-Premotor Mirror Neuron Regions.

To probe the presence of mirror neurons in the human brain, cross-modal fMRI adaptation has been suggested as a suitable technique. The rationale behind this suggestion is that this technique allows making more accurate inferences about neural response properties underlying fMRI voxel activations, beyond merely showing shared voxels that are active during both action observation and execution. However, the validity of using cross-modal fMRI adaptation to demonstrate the presence of mirror neurons in parietal and premotor brain regions has been questioned given the inconsistent and weak results obtained in human studies. A better understanding of cross-modal fMRI adaptation effects in the macaque brain is required as the rationale for using this approach is based on several assumptions related to macaque mirror neuron response properties that still need validation. Here, we conducted a cross-modal fMRI adaptation study in macaque monkeys, using the same action execution and action observation tasks that successfully yielded mirror neuron region cross-modal action decoding in a previous monkey MVPA study. We scanned two male rhesus monkeys while they first executed a sequence of either reach-and-grasp or reach-and-touch hand actions and then observed a video of a human actor performing these motor acts. Both whole-brain and region-of-interest analyses failed to demonstrate cross-modal fMRI adaptation effects in parietal and premotor mirror neuron regions. Our results, in line with previous findings in non-human primates, show that cross-modal motor-to-visual fMRI adaptation is not easily detected in monkey brain regions known to house mirror neurons. Thus, our results advocate caution in using cross-modal fMRI adaptation as a method to infer whether mirror neurons can be found in the primate brain.

A parcellation scheme of mouse isocortex based on reversals in connectivity gradients.

The brain is composed of several anatomically clearly separated structures. This parcellation is often extended into the isocortex, based on anatomical, physiological, or functional differences. Here, we derive a parcellation scheme based purely on the spatial structure of long-range synaptic connections within the cortex. To that end, we analyzed a publicly available dataset of average mouse brain connectivity, and split the isocortex into disjunct regions. Instead of clustering connectivity based on modularity, our scheme is inspired by methods that split sensory cortices into subregions where gradients of neuronal response properties, such as the location of the receptive field, reverse. We calculated comparable gradients from voxelized brain connectivity data and automatically detected reversals in them. This approach better respects the known presence of functional gradients within brain regions than clustering-based approaches. Placing borders at the reversals resulted in a parcellation into 41 subregions that differs significantly from an established scheme in nonrandom ways, but is comparable in terms of the modularity of connectivity between regions. It reveals unexpected trends of connectivity, such as a tripartite split of somatomotor regions along an anterior to posterior gradient. The method can be readily adapted to other organisms and data sources, such as human functional connectivity.

Active cortical networks promote shunting fast synaptic inhibition in vivo

Fast synaptic inhibition determines neuronal response properties in the mammalian brain and is mediated by chloride-permeable ionotropic GABA-A receptors (GABAARs). Despite their fundamental role, it is still not known how GABAARs signal in the intact brain. Here, we use invivo gramicidin recordings to investigate synaptic GABAAR signaling in mouse cortical pyramidal neurons under conditions that preserve native transmembrane chloride gradients. In anesthetized cortex, synaptic GABAARs exert classic hyperpolarizing effects. In contrast, GABAAR-mediated synaptic signaling in awake cortex is found to be predominantly shunting. This is due to more depolarized GABAAR equilibrium potentials (EGABAAR), which are shown to result from the high levels of synaptic activity that characterize awake cortical networks. Synaptic EGABAAR observed in awake cortex facilitates the desynchronizing effects of inhibitory inputs upon local networks, which increases the flexibility of spiking responses to external inputs. Our findings therefore suggest that GABAAR signaling adapts to optimize cortical functions.

Enhancement of phase-locking in rodents. II. An axonal recording study in chinchilla.

The trapezoid body (TB) contains axons of neurons residing in the anteroventral cochlear nucleus (AVCN) which provide excitatory and inhibitory inputs to the main monaural and binaural nuclei in the superior olivary complex (SOC). To understand the monaural and binaural response properties of neurons in the medial and lateral superior olive (MSO and LSO), it is important to characterize the temporal firing properties of these inputs. Because of its exceptional low-frequency hearing, the chinchilla (Chinchilla lanigera) is one of the widely used small animal models for studies of hearing. However, the characterization of the output of its ventral cochlear nucleus to the nuclei of the SOC is fragmentary. We obtained responses of TB axons to stimuli typically used in binaural studies and compared these responses to those of auditory nerve (AN) fibers, with a focus on temporal coding. We found enhancement of phase-locking and entrainment, i.e. the ability of a neuron to fire action potentials at a certain stimulus phase for nearly every stimulus period, in TB axons relative to AN fibers. Enhancement in phase-locking and entrainment are quantitatively more modest than in the cat but greater than in the gerbil. As in these species, these phenomena occur not only in low-frequency neurons stimulated at their characteristic frequency, but also in neurons tuned to higher frequencies when stimulated with low-frequency tones, to which complex phase-locking behavior with multiple modes of firing per stimulus cycle is frequently observed.

Dynamic Recruitment of the Feedforward and Recurrent Mechanism for Black-White Asymmetry in the Primary Visual Cortex.

Black and white information is asymmetrically distributed in natural scenes, evokes asymmetric neuronal responses, and causes asymmetric perceptions. Recognizing the universality and essentiality of black-white asymmetry in visual information processing, the neural substrates for black-white asymmetry remain unclear. To disentangle the role of the feedforward and recurrent mechanisms in the generation of cortical black-white asymmetry, we recorded the V1 laminar responses and LGN responses of anesthetized cats of both sexes. In a cortical column, we found that black-white asymmetry starts at the input layer and becomes more pronounced in the output layer. We also found distinct dynamics of black-white asymmetry between the output layer and the input layer. Specifically, black responses dominate in all layers after stimulus onset. After stimulus offset, black and white responses are balanced in the input layer, but black responses still dominate in the output layer. Compared with that in the input layer, the rebound response in the output layer is significantly suppressed. The relative suppression strength evoked by white stimuli is notably stronger and depends on the location within the ON-OFF cortical map. A model with delayed and polarity-selective cortical suppression explains black-white asymmetry in the output layer, within which prominent recurrent connections are identified by Granger causality analysis. In addition to black-white asymmetry in response strength, the interlaminar differences in spatial receptive field varied dynamically. Our findings suggest that the feedforward and recurrent mechanisms are dynamically recruited for the generation of black-white asymmetry in V1.SIGNIFICANCE STATEMENT Black-white asymmetry is universal and essential in visual information processing, yet the neural substrates for cortical black-white asymmetry remain unknown. Leveraging V1 laminar recordings, we provided the first laminar pattern of black-white asymmetry in cat V1 and found distinct dynamics of black-white asymmetry between the output layer and the input layer. Comparing black-white asymmetry across three visual hierarchies, the LGN, V1 input layer, and V1 output layer, we demonstrated that the feedforward and recurrent mechanisms are dynamically recruited for the generation of cortical black-white asymmetry. Our findings not only enhance our understanding of laminar processing within a cortical column but also elucidate how feedforward connections and recurrent connections interact to shape neuronal response properties.

Distinct topographic organization and network activity patterns of corticocollicular neurons within layer 5 auditory cortex.

The auditory cortex (AC) modulates the activity of upstream pathways in the auditory brainstem via descending (corticofugal) projections. This feedback system plays an important role in the plasticity of the auditory system by shaping response properties of neurons in many subcortical nuclei. The majority of layer (L) 5 corticofugal neurons project to the inferior colliculus (IC). This corticocollicular (CC) pathway is involved in processing of complex sounds, auditory-related learning, and defense behavior. Partly due to their location in deep cortical layers, CC neuron population activity patterns within neuronal AC ensembles remain poorly understood. We employed two-photon imaging to record the activity of hundreds of L5 neurons in anesthetized as well as awake animals. CC neurons are broader tuned than other L5 pyramidal neurons and display weaker topographic order in core AC subfields. Network activity analyses revealed stronger clusters of CC neurons compared to non-CC neurons, which respond more reliable and integrate information over larger distances. However, results obtained from secondary auditory cortex (A2) differed considerably. Here CC neurons displayed similar or higher topography, depending on the subset of neurons analyzed. Furthermore, specifically in A2, CC activity clusters formed in response to complex sounds were spatially more restricted compared to other L5 neurons. Our findings indicate distinct network mechanism of CC neurons in analyzing sound properties with pronounced subfield differences, demonstrating that the topography of sound-evoked responses within AC is neuron-type dependent.

Descending Facilitation of Nociceptive Transmission From the Rostral Ventromedial Medulla Contributes to Hyperalgesia in Mice with Sickle Cell Disease

Sickle cell disease (SCD) is an inherited blood disorder that is associated with acute episodic and chronic pain. Mice with SCD have robust hyperalgesia mediated, in part, by sensitization of spinal dorsal horn neurons. However, underlying mechanisms are not fully understood. Since the rostral ventromedial medulla (RVM) is a major component of descending circuitry that modulates nociceptive transmission in the spinal cord, we examined if the RVM contributes to hyperalgesia in mice with SCD. Injection of lidocaine, but not vehicle, into the RVM eliminated mechanical and heat hyperalgesia in sickle (HbSS-BERK) mice without altering mechanical and heat sensitivity in naïve C57B mice. These data indicate that the RVM contributes to the maintenance of hyperalgesia in mice with SCD. In electrophysiological studies, we determined the changes in response properties of RVM neurons that might contribute to hyperalgesia in sickle mice. Recordings were made from single ON, OFF, and Neutral cells in the RVM of sickle and control (HbAA-BERK) mice. Spontaneous activity and responses of ON, OFF and Neutral cells evoked by heat (50 °C) and mechanical (26 g) stimuli applied to the hind paw were compared between sickle and control mice. Although there were no differences in the proportions of functionally-identified neurons or spontaneous activity between sickle and control mice, evoked responses of ON cells to heat and mechanical stimuli were increased approximately 3-fold in sickle mice as compared to control mice. Thus, the RVM contributes to hyperalgesia in sickle mice via a specific ON cell-dependent descending facilitation of nociceptive transmission.

Fast-Spiking Interneurons of the Premotor Cortex Contribute to Initiation and Execution of Spontaneous Actions.

Planning and execution of voluntary movement depend on the contribution of distinct classes of neurons in primary motor and premotor areas. However, timing and pattern of activation of GABAergic cells during specific motor behaviors remain only partly understood. Here, we directly compared the response properties of putative pyramidal neurons (PNs) and GABAergic fast-spiking neurons (FSNs) during spontaneous licking and forelimb movements in male mice. Recordings centered on the face/mouth motor field of the anterolateral motor cortex (ALM) revealed that FSNs fire longer than PNs and earlier for licking, but not for forelimb movements. Computational analysis revealed that FSNs carry vastly more information than PNs about the onset of movement. While PNs differently modulate their discharge during distinct motor acts, most FSNs respond with a stereotyped increase in firing rate. Accordingly, the informational redundancy was greater among FSNs than PNs. Finally, optogenetic silencing of a subset of FSNs reduced spontaneous licking movement. These data suggest that a global rise of inhibition contributes to the initiation and execution of spontaneous motor actions.SIGNIFICANCE STATEMENT Our study contributes to clarifying the causal role of fast-spiking neurons (FSNs) in driving initiation and execution of specific, spontaneous movements. Within the face/mouth motor field of mice premotor cortex, FSNs fire before pyramidal neurons (PNs) with a specific activation pattern: they reach their peak of activity earlier than PNs during the initiation of licking, but not of forelimb, movements; duration of FSNs activity is also greater and exhibits less selectivity for the movement type, as compared with that of PNs. Accordingly, FSNs appear to carry more redundant information than PNs. Optogenetic silencing of FSNs reduced spontaneous licking movement, suggesting that FSNs contribute to the initiation and execution of specific spontaneous movements, possibly by sculpting response selectivity of nearby PNs.

Neuronal Spiking Responses to Direct Electrical Microstimulation in the Human Cortex.

Microstimulation can modulate the activity of individual neurons to affect behavior, but the effects of stimulation on neuronal spiking are complex and remain poorly understood. This is especially challenging in the human brain where the response properties of individual neurons are sparse and heterogeneous. Here we use microelectrode arrays in the human anterior temporal lobe in 6 participants (3 female) to examine the spiking responses of individual neurons to microstimulation delivered through multiple distinct stimulation sites. We demonstrate that individual neurons can be driven with excitation or inhibition using different stimulation sites, which suggests an approach for providing direct control of spiking activity at the single-neuron level. Spiking responses are inhibitory in neurons that are close to the site of stimulation, while excitatory responses are more spatially distributed. Together, our data demonstrate that spiking responses of individual neurons can be reliably identified and manipulated in the human cortex.SIGNIFICANCE STATEMENT One of the major limitations in our ability to interface directly with the human brain is that the effects of stimulation on the activity of individual neurons remain poorly understood. This study examines the spiking responses of neurons in the human temporal cortex in response to pulses of microstimulation. This study finds that individual neurons can either be excited or inhibited depending on the site of stimulation. These data suggest an approach for modulating the spiking activity of individual neurons in the human brain.

A convolutional neural network provides a generalizable model of natural sound coding by neural populations in auditory cortex.

Convolutional neural networks (CNNs) can provide powerful and flexible models of neural sensory processing. However, the utility of CNNs in studying the auditory system has been limited by their requirement for large datasets and the complex response properties of single auditory neurons. To address these limitations, we developed a population encoding model: a CNN that simultaneously predicts activity of several hundred neurons recorded during presentation of a large set of natural sounds. This approach defines a shared spectro-temporal space and pools statistical power across neurons. Population models of varying architecture performed consistently and substantially better than traditional linear-nonlinear models on data from primary and non-primary auditory cortex. Moreover, population models were highly generalizable. The output layer of a model pre-trained on one population of neurons could be fit to data from novel single units, achieving performance equivalent to that of neurons in the original fit data. This ability to generalize suggests that population encoding models capture a complete representational space across neurons in an auditory cortical field.

Monocular deprivation during the critical period alters neuronal tuning and the composition of visual circuitry.

Abnormal visual experience during a developmental critical period degrades cortical responsiveness. Yet how experience-dependent plasticity alters the response properties of individual neurons and composition of visual circuitry is unclear. Here, we measured with calcium imaging in alert mice how monocular deprivation (MD) during the developmental critical period affects tuning for binocularity, orientation, and spatial frequency for neurons in primary visual cortex. MD of the contralateral eye did not uniformly shift ocular dominance (OD) of neurons towards the fellow ipsilateral eye but reduced the number of monocular contralateral neurons and increased the number of monocular ipsilateral neurons. MD also impaired matching of preferred orientation for binocular neurons and reduced the percentage of neurons responsive at most spatial frequencies for the deprived contralateral eye. Tracking the tuning properties for several hundred neurons before and after MD revealed that the shift in OD is complex and dynamic, with many previously monocular neurons becoming binocular and binocular neurons becoming monocular. Binocular neurons that became monocular were more likely to lose responsiveness to the deprived contralateral eye if they were better matched for orientation prior to deprivation. In addition, the composition of visual circuitry changed as population of neurons more responsive to the deprived eye were exchanged for neurons with tuning properties more similar to the network of responsive neurons altered by MD. Thus, plasticity during the critical period adapts to recent experience by both altering the tuning of responsive neurons and recruiting neurons with matching tuning properties.

Efficient multi-scale representation of visual objects using a biologically plausible spike-latency code and winner-take-all inhibition

Deep neural networks have surpassed human performance in key visual challenges such as object recognition, but require a large amount of energy, computation, and memory. In contrast, spiking neural networks (SNNs) have the potential to improve both the efficiency and biological plausibility of object recognition systems. Here we present a SNN model that uses spike-latency coding and winner-take-all inhibition (WTA-I) to efficiently represent visual stimuli using multi-scale parallel processing. Mimicking neuronal response properties in early visual cortex, images were preprocessed with three different spatial frequency (SF) channels, before they were fed to a layer of spiking neurons whose synaptic weights were updated using spike-timing-dependent-plasticity. We investigate how the quality of the represented objects changes under different SF bands and WTA-I schemes. We demonstrate that a network of 200 spiking neurons tuned to three SFs can efficiently represent objects with as little as 15 spikes per neuron. Studying how core object recognition may be implemented using biologically plausible learning rules in SNNs may not only further our understanding of the brain, but also lead to novel and efficient artificial vision systems.

Surround suppression in mouse auditory cortex underlies auditory edge detection.

Surround suppression (SS) is a fundamental property of sensory processing throughout the brain. In the auditory system, the early processing stream encodes sounds using a one dimensional physical space-frequency. Previous studies in the auditory system have shown SS to manifest as bandwidth tuning around the preferred frequency. We asked whether bandwidth tuning can be found around frequencies away from the preferred frequency. We exploited the simplicity of spectral representation of sounds to study SS by manipulating both sound frequency and bandwidth. We recorded single unit spiking activity from the auditory cortex (ACx) of awake mice in response to an array of broadband stimuli with varying central frequencies and bandwidths. Our recordings revealed that a significant portion of neuronal response profiles had a preferred bandwidth that varied in a regular way with the sound's central frequency. To gain insight into the possible mechanism underlying these responses, we modelled neuronal activity using a variation of the "Mexican hat" function often used to model SS. The model accounted for response properties of single neurons with high accuracy. Our data and model show that these responses in ACx obey simple rules resulting from the presence of lateral inhibitory sidebands, mostly above the excitatory band of the neuron, that result in sensitivity to the location of top frequency edges, invariant to other spectral attributes. Our work offers a simple explanation for auditory edge detection and possibly other computations of spectral content in sounds.

Brain State-Dependent Modulation of Thalamic Visual Processing by Cortico-Thalamic Feedback.

The behavioral state of a mammal impacts how the brain responds to visual stimuli as early as in the dorsolateral geniculate nucleus of the thalamus (dLGN), the primary relay of visual information to the cortex. A clear example of this is the markedly stronger response of dLGN neurons to higher temporal frequencies of the visual stimulus in alert as compared with quiescent animals. The dLGN receives strong feedback from the visual cortex, yet whether this feedback contributes to these state-dependent responses to visual stimuli is poorly understood. Here, we show that in male and female mice, silencing cortico-thalamic feedback profoundly reduces state-dependent differences in the response of dLGN neurons to visual stimuli. This holds true for dLGN responses to both temporal and spatial features of the visual stimulus. These results reveal that the state-dependent shift of the response to visual stimuli in an early stage of visual processing depends on cortico-thalamic feedback.SIGNIFICANCE STATEMENT Brain state affects even the earliest stages of sensory processing. A clear example of this phenomenon is the change in thalamic responses to visual stimuli depending on whether the animal's brain is in an alert or quiescent state. Despite the radical impact that brain state has on sensory processing, the underlying circuits are still poorly understood. Here, we show that both the temporal and spatial response properties of thalamic neurons to visual stimuli depend on the state of the animal and, crucially, that this state-dependent shift relies on the feedback projection from visual cortex to thalamus.