Inhibitory Gating of Thalamocortical Inputs onto Rat Gustatory Insular Cortex.

In primary gustatory cortex (GC), a subregion of the insular cortex, neurons show anticipatory activity, encode taste identity and palatability, and their activity is related to decision-making. Inactivation of the gustatory thalamus, the parvicellular region of the ventral posteromedial thalamic nucleus (VPMpc), dramatically reduces GC taste responses, consistent with the hypothesis that VPMpc-GC projections carry taste information. Recordings in awake rodents reported that taste-responsive neurons can be found across GC, without segregated spatial mapping, raising the possibility that projections from the taste thalamus may activate GC broadly. In addition, we have shown that cortical inhibition modulates the integration of thalamic and limbic inputs, revealing a potential role for GABA transmission in gating sensory information to GC. Despite this wealth of information at the system level, the synaptic organization of the VPMpc-GC circuit has not been investigated. Here, we used optogenetic activation of VPMpc afferents to GC in acute slice preparations from rats of both sexes to investigate the synaptic properties and organization of VPMpc afferents in GC and their modulation by cortical inhibition. We hypothesized that VPMpc-GC synapses are distributed across GC, but show laminar- and cell-specific properties, conferring computationally flexibility to how taste information is processed. We also found that VPMpc-GC synaptic responses are strongly modulated by the activity regimen of VPMpc afferents, as well as by cortical inhibition activating GABAA and GABAB receptors onto VPMpc terminals. These results provide a novel insight into the complex features of thalamocortical circuits for taste processing.SIGNIFICANCE STATEMENT We report that the input from the primary taste thalamus to the primary gustatory cortex (GC) shows distinct properties compared with primary thalamocortical synapses onto other sensory areas. Ventral posteromedial thalamic nucleus afferents in GC make synapses with excitatory neurons distributed across all cortical layers and display frequency-dependent short-term plasticity to repetitive stimulation; thus, they do not fit the classic distinction between drivers and modulators typical of other sensory thalamocortical circuits. Thalamocortical activation of GC is gated by cortical inhibition, providing local corticothalamic feedback via presynaptic ionotropic and metabotropic GABA receptors. The connectivity and inhibitory control of thalamocortical synapses in GC highlight unique features of the thalamocortical circuit for taste.

Temporal progression along discrete coding states during decision-making in the mouse gustatory cortex.

The mouse gustatory cortex (GC) is involved in taste-guided decision-making in addition to sensory processing. Rodent GC exhibits metastable neural dynamics during ongoing and stimulus-evoked activity, but how these dynamics evolve in the context of a taste-based decision-making task remains unclear. Here we employ analytical and modeling approaches to i) extract metastable dynamics in ensemble spiking activity recorded from the GC of mice performing a perceptual decision-making task; ii) investigate the computational mechanisms underlying GC metastability in this task; and iii) establish a relationship between GC dynamics and behavioral performance. Our results show that activity in GC during perceptual decision-making is metastable and that this metastability may serve as a substrate for sequentially encoding sensory, abstract cue, and decision information over time. Perturbations of the model's metastable dynamics indicate that boosting inhibition in different coding epochs differentially impacts network performance, explaining a counterintuitive effect of GC optogenetic silencing on mouse behavior.

Layer- and Cell Type-Specific Response Properties of Gustatory Cortex Neurons in Awake Mice.

Studies in visual, auditory, and somatosensory cortices have revealed that different cell types as well as neurons located in different laminae display distinct stimulus response profiles. The extent to which these layer and cell type-specific distinctions generalize to gustatory cortex (GC) remains unknown. In this study, we performed extracellular recordings in adult female mice to monitor the activity of putative pyramidal and inhibitory neurons located in deep and superficial layers of GC. Awake, head-restrained mice were trained to lick different tastants (sucrose, salt, citric acid, quinine, and water) from a lick spout. We found that deep layer neurons show higher baseline firing rates (FRs) in GC with deep-layer inhibitory neurons displaying highest FRs at baseline and following the stimulus. GC's activity shows robust modulations before animals' contact with tastants, and this phenomenon is most prevalent in deep-layer inhibitory neurons. Furthermore, we show that licking activity strongly shapes the spiking pattern of GC pyramidal neurons, eliciting phase-locked spiking across trials and tastants. We demonstrate that there is a greater percentage of taste-coding neurons in deep versus superficial layers with chemosensitive neurons across all categories showing similar breadth of tuning, but different decoding performance. Lastly, we provide evidence for functional convergence in GC, with neurons that can show prestimulus activity, licking-related rhythmicity and taste responses. Overall, our results demonstrate that baseline and stimulus-evoked firing profiles of GC neurons and their processing schemes change as a function of cortical layer and cell type in awake mice.SIGNIFICANCE STATEMENT Sensory cortical areas show a laminar structure, with each layer composed of distinct cell types embedded in different circuits. While studies in other primary sensory areas have elucidated that pyramidal and inhibitory neurons belonging to distinct layers show distinct response properties, whether and how response properties of gustatory cortex (GC) neurons change as a function of their laminar position and cell type remains uninvestigated. Here, we show that there are several notable differences in baseline, prestimulus, and stimulus-evoked response profiles of pyramidal and inhibitory neurons belonging to deep and superficial layers of GC.

Disruption of Cortical Dopaminergic Modulation Impairs Preparatory Activity and Delays Licking Initiation.

Dysfunction of motor cortices is thought to contribute to motor disorders such as Parkinson's disease (PD). However, little is known on the link between cortical dopaminergic loss, abnormalities in motor cortex neural activity and motor deficits. We address the role of dopamine in modulating motor cortical activity by focusing on the anterior lateral motor cortex (ALM) of mice performing a cued-licking task. We first demonstrate licking deficits and concurrent alterations of spiking activity in ALM of head-fixed mice with unilateral depletion of dopaminergic neurons (i.e., mice injected with 6-OHDA into the medial forebrain bundle). Hemilesioned mice displayed delayed licking initiation, shorter duration of licking bouts, and lateral deviation of tongue protrusions. In parallel with these motor deficits, we observed a reduction in the prevalence of cue responsive neurons and altered preparatory activity. Acute and local blockade of D1 receptors in ALM recapitulated some of the key behavioral and neural deficits observed in hemilesioned mice. Altogether, our data show a direct relationship between cortical D1 receptor modulation, cue-evoked, and preparatory activity in ALM, and licking initiation.

Processing of Intraoral Olfactory and Gustatory Signals in the Gustatory Cortex of Awake Rats.

The integration of gustatory and olfactory information is essential to the perception of flavor. Human neuroimaging experiments have pointed to the gustatory cortex (GC) as one of the areas involved in mediating flavor perception. Although GC's involvement in encoding the chemical identity and hedonic value of taste stimuli is well studied, it is unknown how single GC neurons process olfactory stimuli emanating from the mouth. In this study, we relied on multielectrode recordings to investigate how single GC neurons respond to intraorally delivered tastants and tasteless odorants dissolved in water and whether/how these two modalities converge in the same neurons. We found that GC neurons could either be unimodal, responding exclusively to taste (taste-only) or odor (odor-only), or bimodal, responding to both gustatory and olfactory stimuli. Odor responses were confirmed to result from retronasal olfaction: monitoring respiration revealed that exhalation preceded odor-evoked activity and reversible inactivation of olfactory receptors in the nasal epithelium significantly reduced responses to intraoral odorants but not to tastants. Analysis of bimodal neurons revealed that they encode palatability significantly better than the unimodal taste-only group. Bimodal neurons exhibited similar responses to palatable tastants and odorants dissolved in water. This result suggested that odorized water could be palatable. This interpretation was further supported with a brief access task, where rats avoided consuming aversive taste stimuli and consumed the palatable tastants and dissolved odorants. These results demonstrate the convergence of the chemosensory components of flavor onto single GC neurons and provide evidence for the integration of flavor with palatability coding. SIGNIFICANCE STATEMENT: Food perception and choice depend upon the concurrent processing of olfactory and gustatory signals from the mouth. The primary gustatory cortex has been proposed to integrate chemosensory stimuli; however, no study has examined the single-unit responses to intraoral odorant presentation. Here we found that neurons in gustatory cortex can respond either exclusively to tastants, exclusively to odorants, or to both (bimodal). Several differences exist between these groups' responses; notably, bimodal neurons code palatability significantly better than unimodal neurons. This group of neurons might represent a substrate for how odorants gain the quality of tastants.

Central role for the insular cortex in mediating conditioned responses to anticipatory cues.

Reward-related circuits are fundamental for initiating feeding on the basis of food-predicting cues, whereas gustatory circuits are believed to be involved in the evaluation of food during consumption. However, accumulating evidence challenges such a rigid separation. The insular cortex (IC), an area largely studied in rodents for its role in taste processing, is involved in representing anticipatory cues. Although IC responses to anticipatory cues are well established, the role of IC cue-related activity in mediating feeding behaviors is poorly understood. Here, we examined the involvement of the IC in the expression of cue-triggered food approach in mice trained with a Pavlovian conditioning paradigm. We observed a significant change in neuronal firing during presentation of the cue. Pharmacological silencing of the IC inhibited food port approach. Such a behavior could be recapitulated by temporally selective inactivation during the cue. These findings represent the first evidence, to our knowledge, that cue-evoked neuronal activity in the mouse IC modulates behavioral output, and demonstrate a causal link between cue responses and feeding behaviors.

Laminar- and Target-Specific Amygdalar Inputs in Rat Primary Gustatory Cortex.

The primary gustatory cortex (GC) receives projections from the basolateral nucleus of the amygdala (BLA). Behavioral and electrophysiological studies demonstrated that this projection is involved in encoding the hedonic value of taste and is a source of anticipatory activity in GC. Anatomically, this projection is largest in the agranular portion of GC; however, its synaptic targets and synaptic properties are currently unknown. In vivo electrophysiological recordings report conflicting evidence about BLA afferents either selectively activating excitatory neurons or driving a compound response consistent with the activation of inhibitory circuits. Here we demonstrate that BLA afferents directly activate excitatory neurons and two distinct populations of inhibitory neurons in both superficial and deep layers of rat GC. BLA afferents recruit different proportions of excitatory and inhibitory neurons and show distinct patterns of circuit activation in the superficial and deep layers of GC. These results provide the first circuit-level analysis of BLA inputs to a sensory area. Laminar- and target-specific differences of BLA inputs likely explain the complexity of amygdalocortical interactions during sensory processing. SIGNIFICANCE STATEMENT: Projections from the basolateral nucleus of the amygdala (BLA) to the cortex convey information about the emotional value and the expectation of a sensory stimulus. Although much work has been done to establish the behavioral role of BLA inputs to sensory cortices, very little is known about the circuit organization of BLA projections. Here we provide the first in-depth analysis of connectivity and synaptic properties of the BLA input to the gustatory cortex. We show that BLA afferents activate excitatory and inhibitory circuits in a layer-specific and pattern-specific manner. Our results provide important new information about how neural circuits establishing the hedonic value of sensory stimuli and driving anticipatory behaviors are organized at the synaptic level.

State Dependency of Chemosensory Coding in the Gustatory Thalamus (VPMpc) of Alert Rats.

The parvicellular portion of the ventroposteromedial nucleus (VPMpc) is the part of the thalamus that processes gustatory information. Anatomical evidence shows that the VPMpc receives ascending gustatory inputs from the parabrachial nucleus (PbN) in the brainstem and sends projections to the gustatory cortex (GC). Although taste processing in PbN and GC has been the subject of intense investigation in behaving rodents, much less is known on how VPMpc neurons encode gustatory information. Here we present results from single-unit recordings in the VPMpc of alert rats receiving multiple tastants. Thalamic neurons respond to taste with time-varying modulations of firing rates, consistent with those observed in GC and PbN. These responses encode taste quality as well as palatability. Comparing responses to tastants either passively delivered, or self-administered after a cue, unveiled the effects of general expectation on taste processing in VPMpc. General expectation led to an improvement of taste coding by modulating response dynamics, and single neuron ability to encode multiple tastants. Our results demonstrate that the time course of taste coding as well as single neurons' ability to encode for multiple qualities are not fixed but rather can be altered by the state of the animal. Together, the data presented here provide the first description that taste coding in VPMpc is dynamic and state-dependent. SIGNIFICANCE STATEMENT: Over the past years, a great deal of attention has been devoted to understanding taste coding in the brainstem and cortex of alert rodents. Thanks to this research, we now know that taste coding is dynamic, distributed, and context-dependent. Alas, virtually nothing is known on how the gustatory thalamus (VPMpc) processes gustatory information in behaving rats. This manuscript investigates taste processing in the VPMpc of behaving rats. Our results show that thalamic neurons encode taste and palatability with time-varying patterns of activity and that thalamic coding of taste is modulated by general expectation. Our data will appeal not only to researchers interested in taste, but also to a broader audience of sensory and systems neuroscientists interested in the thalamocortical system.

Dynamics of multistable states during ongoing and evoked cortical activity.

Single-trial analyses of ensemble activity in alert animals demonstrate that cortical circuits dynamics evolve through temporal sequences of metastable states. Metastability has been studied for its potential role in sensory coding, memory, and decision-making. Yet, very little is known about the network mechanisms responsible for its genesis. It is often assumed that the onset of state sequences is triggered by an external stimulus. Here we show that state sequences can be observed also in the absence of overt sensory stimulation. Analysis of multielectrode recordings from the gustatory cortex of alert rats revealed ongoing sequences of states, where single neurons spontaneously attain several firing rates across different states. This single-neuron multistability represents a challenge to existing spiking network models, where typically each neuron is at most bistable. We present a recurrent spiking network model that accounts for both the spontaneous generation of state sequences and the multistability in single-neuron firing rates. Each state results from the activation of neural clusters with potentiated intracluster connections, with the firing rate in each cluster depending on the number of active clusters. Simulations show that the model's ensemble activity hops among the different states, reproducing the ongoing dynamics observed in the data. When probed with external stimuli, the model predicts the quenching of single-neuron multistability into bistability and the reduction of trial-by-trial variability. Both predictions were confirmed in the data. Together, these results provide a theoretical framework that captures both ongoing and evoked network dynamics in a single mechanistic model.

Encoding and tracking of outcome-specific expectancy in the gustatory cortex of alert rats.

In natural conditions, gustatory stimuli are typically expected. Anticipatory and contextual cues provide information that allows animals to predict the availability and the identity of the substance to be ingested. Recording in alert rats trained to self-administer tastants following a go signal revealed that neurons in the primary gustatory cortex (GC) can respond to anticipatory cues. These experiments were optimized to demonstrate that even the most general form of expectation can activate neurons in GC, and did not provide indications on whether cues predicting different tastants could be encoded selectively by GC neurons. Here we recorded single-neuron activity in GC of rats engaged in a task where one auditory cue predicted sucrose, while another predicted quinine. We found that GC neurons respond differentially to the two cues. Cue-selective responses develop in parallel with learning. Comparison between cue and sucrose responses revealed that cues could trigger the activation of anticipatory representations. Additional experiments showed that an expectation of sucrose leads a subset of neurons to produce sucrose-like responses even when the tastant was omitted. Altogether, the data show that primary sensory cortices can encode for cues predicting different outcomes, and that specific expectations result in the activation of anticipatory representations.

Thalamic contribution to cortical processing of taste and expectation.

Taste-related information reaches the gustatory cortex (GC) through two routes: a thalamic and a limbic pathway. While evidence is accumulating on limbic-cortical interactions in taste, very little information is available on the function of the gustatory thalamus in shaping GC activity. Here we rely on behavioral electrophysiological techniques to study taste-evoked activity in GC before and after inactivation of the parvicellular portion of the ventroposteromedial nucleus of thalamus (VPMpc; i.e., the gustatory thalamus). Gustatory stimuli were presented to rats either alone or preceded by an anticipatory cue. The reliance on two different behavioral contexts allowed us to investigate how the VPMpc mediates GC responses to uncued tastants, cued tastants, and anticipatory cues. Inactivation of the thalamus resulted in a dramatic reduction of taste processing in GC. However, responses to anticipatory cues were unaffected by this manipulation. The use of a cue-taste association paradigm also allowed for the identification of two subpopulations of taste-specific neurons: those that responded to gustatory stimulation and to the cue (i.e., cue-and-taste) and those that responded to tastants only (i.e., taste-only). Analyses of these two populations revealed differences in response dynamics and connectivity with the VPMpc. The results provide novel evidence for the role of VPMpc in shaping GC activity and demonstrate a previously unknown association between responsiveness to behavioral events, temporal dynamics, and thalamic connectivity in GC.

Processing of hedonic and chemosensory features of taste in medial prefrontal and insular networks.

Most of the research on cortical processing of taste has focused on either the primary gustatory cortex (GC) or the orbitofrontal cortex (OFC). However, these are not the only areas involved in taste processing. Gustatory information can also reach another frontal region, the medial prefrontal cortex (mPFC), via direct projections from GC. mPFC has been studied extensively in relation to its role in controlling goal-directed action and reward-guided behaviors, yet very little is known about its involvement in taste coding. The experiments presented here address this important point and test whether neurons in mPFC can significantly process the physiochemical and hedonic dimensions of taste. Spiking responses to intraorally delivered tastants were recorded from rats implanted with bundles of electrodes in mPFC and GC. Analysis of single-neuron and ensemble activity revealed similarities and differences between the two areas. Neurons in mPFC can encode the chemosensory identity of gustatory stimuli. However, responses in mPFC are sparser, more narrowly tuned, and have a later onset than in GC. Although taste quality is more robustly represented in GC, taste palatability is coded equally well in the two areas. Additional analysis of responses in neurons processing the hedonic value of taste revealed differences between the two areas in temporal dynamics and sensitivities to palatability. These results add mPFC to the network of areas involved in processing gustatory stimuli and demonstrate significant differences in taste-coding between GC and mPFC.

Learning enhances representations of taste-guided decisions in the mouse gustatory insular cortex.

Learning to discriminate overlapping gustatory stimuli that predict distinct outcomes-a feat known as discrimination learning-can mean the difference between ingesting a poison or a nutritive meal. Despite the obvious importance of this process, very little is known about the neural basis of taste discrimination learning. In other sensory modalities, this form of learning can be mediated by either the sharpening of sensory representations or the enhanced ability of "decision-making" circuits to interpret sensory information. Given the dual role of the gustatory insular cortex (GC) in encoding both sensory and decision-related variables, this region represents an ideal site for investigating how neural activity changes as animals learn a novel taste discrimination. Here, we present results from experiments relying on two-photon calcium imaging of GC neural activity in mice performing a taste-guided mixture discrimination task. The task allows for the recording of neural activity before and after learning induced by training mice to discriminate increasingly similar pairs of taste mixtures. Single-neuron and population analyses show a time-varying pattern of activity, with early sensory responses emerging after taste delivery and binary, choice-encoding responses emerging later in the delay before a decision is made. Our results demonstrate that, while both sensory and decision-related information is encoded by GC in the context of a taste mixture discrimination task, learning and improved performance are associated with a specific enhancement of decision-related responses.

Experience-dependent switch in sign and mechanisms for plasticity in layer 4 of primary visual cortex.

Neural circuits are extensively refined by sensory experience during postnatal development. How the maturation of recurrent cortical synapses may contribute to events regulating the postnatal refinement of neocortical microcircuits remains controversial. Here we show that, in the main input layer of rat primary visual cortex, layer 4 (L4), recurrent excitatory synapses are endowed with multiple, developmentally regulated mechanisms for induction and expression of excitatory synaptic plasticity. Maturation of L4 synapses and visual experience lead to a sharp switch in sign and mechanisms for plasticity at recurrent excitatory synapses in L4 at the onset of the critical period for visual cortical plasticity. The state of maturation of excitatory pyramidal neurons allows neurons to engage different mechanisms for plasticity in response to the same induction paradigm. Experience is determinant for the maturation of L4 synapses, as well as for the transition between forms of plasticity and the mechanisms they may engage. These results indicate a tight correlation between the effects of sensory drive and maturation on cortical neurons and provide a new set of cellular mechanisms engaged in the postnatal refinement of cortical circuits.

Taste.

In his book on the ecology of perception (An Immense World: How Animal Senses Reveal the Hidden, 2022), science writer Ed Yong emphasizes the simplicity of taste. He writes: "Taste, then, is the simpler sense. As we've seen, smell covers a practically infinite selection of molecules with an indescribably vast range of characteristics, which the nervous system represents through a combinatorial code so fiendish that scientists have barely begun to crack it. Taste, by contrast, boils down to just five basic qualities in humans - salt, sweet, bitter, sour, and umami (savory) - and perhaps a few more in other animals, which are detected through a small number of receptors. And while smell can be put to complex uses - navigating the open oceans, finding prey, and coordinating herds or colonies - taste is almost always used to make binary decisions about food. Yes or no? Good or bad? Consume or spit? It's ironic that we associate taste with connoisseurship, subtlety and fine discrimination when it is among the coarsest of senses."

Learning enhances representations of taste-guided decisions in the mouse gustatory insular cortex.

Learning to discriminate overlapping gustatory stimuli that predict distinct outcomes - a feat known as discrimination learning - can mean the difference between ingesting a poison or a nutritive meal. Despite the obvious importance of this process, very little is known on the neural basis of taste discrimination learning. In other sensory modalities, this form of learning can be mediated by either sharpening of sensory representations, or enhanced ability of "decision-making" circuits to interpret sensory information. Given the dual role of the gustatory insular cortex (GC) in encoding both sensory and decision-related variables, this region represents an ideal site for investigating how neural activity changes as animals learn a novel taste discrimination. Here we present results from experiments relying on two photon calcium imaging of GC neural activity in mice performing a taste-guided mixture discrimination task. The task allows for recording of neural activity before and after learning induced by training mice to discriminate increasingly similar pairs of taste mixtures. Single neuron and population analyses show a time-varying pattern of activity, with early sensory responses emerging after taste delivery and binary, choice encoding responses emerging later in the delay before a decision is made. Our results demonstrate that while both sensory and decision-related information is encoded by GC in the context of a taste mixture discrimination task, learning and improved performance are associated with a specific enhancement of decision-related responses.

Experience-dependent plasticity of gustatory insular cortex circuits and taste preferences.

Early experience with food influences taste preference in adulthood. How gustatory experience influences development of taste preferences and refinement of cortical circuits has not been investigated. Here, we exposed weanling mice to an array of taste solutions and determined the effects on the preference for sweet in adulthood. We demonstrate an experience-dependent shift in sucrose preference persisting several weeks following the termination of exposure. A shift in sucrose palatability, altered neural responsiveness to sucrose, and inhibitory synaptic plasticity in the gustatory portion of the insular cortex (GC) were also induced. The modulation of sweet preference occurred within a restricted developmental window, but restoration of the capacity for inhibitory plasticity in adult GC reactivated the sensitivity of sucrose preference to taste experience. Our results establish a fundamental link between gustatory experience, sweet preference, inhibitory plasticity, and cortical circuit function and highlight the importance of early life nutrition in setting taste preferences.

Cortical networks produce three distinct 7-12 Hz rhythms during single sensory responses in the awake rat.

Cortical rhythms in the alpha/mu frequency range (7-12 Hz) have been variously related to "idling," anticipation, seizure, and short-term or working memory. This overabundance of interpretations suggests that sensory cortex may be able to produce more than one (and even more than two) distinct alpha/mu rhythms. Here we describe simultaneous local field potential and single-neuron recordings made from primary sensory (gustatory) cortex of awake rats and reveal three distinct 7-12 Hz de novo network rhythms within single sessions: an "early," taste-induced approximately 11 Hz rhythm, the first peak of which was a short-latency gustatory evoked potential; a "late," significantly lower-frequency (approximately 7 Hz) rhythm that replaced this first rhythm at approximately 750-850 ms after stimulus onset (consistently timed with a previously described shift in taste temporal codes); and a "spontaneous" spike-and-wave rhythm of intermediate peak frequency (approximately 9 Hz) that appeared late in the session, as part of a oft-described reduction in arousal/attention. These rhythms proved dissociable on many grounds: in addition to having different peak frequencies, amplitudes, and shapes and appearing at different time points (although often within single 3 s snippets of activity), the early and late rhythms proved to have completely uncorrelated session-to-session variability, and the spontaneous rhythm affected the early rhythm only (having no impact on the late rhythm). Analysis of spike-to-wave coupling suggested that the early and late rhythms are a unified part of discriminative taste process: the identity of phase-coupled single-neuron ensembles differed from taste to taste, and coupling typically lasted across the change in frequency. These data reveal that even rhythms confined to a narrow frequency band may still have distinct properties.

Hidden Markov models for the stimulus-response relationships of multistate neural systems.

Given recent experimental results suggesting that neural circuits may evolve through multiple firing states, we develop a framework for estimating state-dependent neural response properties from spike train data. We modify the traditional hidden Markov model (HMM) framework to incorporate stimulus-driven, non-Poisson point-process observations. For maximal flexibility, we allow external, time-varying stimuli and the neurons' own spike histories to drive both the spiking behavior in each state and the transitioning behavior between states. We employ an appropriately modified expectation-maximization algorithm to estimate the model parameters. The expectation step is solved by the standard forward-backward algorithm for HMMs. The maximization step reduces to a set of separable concave optimization problems if the model is restricted slightly. We first test our algorithm on simulated data and are able to fully recover the parameters used to generate the data and accurately recapitulate the sequence of hidden states. We then apply our algorithm to a recently published data set in which the observed neuronal ensembles displayed multistate behavior and show that inclusion of spike history information significantly improves the fit of the model. Additionally, we show that a simple reformulation of the state space of the underlying Markov chain allows us to implement a hybrid half-multistate, half-histogram model that may be more appropriate for capturing the complexity of certain data sets than either a simple HMM or a simple peristimulus time histogram model alone.

Spatially Distributed Representation of Taste Quality in the Gustatory Insular Cortex of Behaving Mice.

Visual, auditory, and somatosensory cortices are topographically organized, with neurons responding to similar sensory features clustering in adjacent portions of the cortex. Such topography has not been observed in the piriform cortex, whose responses to odorants are sparsely distributed across the cortex. The spatial organization of taste responses in the gustatory insular cortex (GC) is currently debated, with conflicting evidence from anesthetized rodents pointing to alternative and mutually exclusive models. Here, we rely on calcium imaging to determine how taste and task-related variables are represented in the superficial layers of GC of alert, licking mice. Our data show that the various stimuli evoke sparse responses from a combination of broadly and narrowly tuned neurons. Analysis of the distribution of responses over multiple spatial scales demonstrates that taste representations are distributed across the cortex, with no sign of spatial clustering or topography. Altogether, data presented here support the idea that the representation of taste qualities in GC of alert mice is sparse and distributed, analogous to the representation of odorants in piriform cortex.