Biology subjects

Fontanini, A.

Publications and source records attributed to Fontanini, A..

11 recordsLinked to original sources

bioRxiv2025

Linear and categorical coding units in the mouse gustatory cortex drive population dynamics and behavior in taste decision-making

Cortical circuits produce time-varying patterns of population and single neuron activity that play a fundamental role in perceptual and behavioral processes. However, the functional contributions of individual neuron activity to population dynamics and behavior remain unclear. Here we addressed this issue focusing on the mouse gustatory cortex (GC) and using a taste mixture-based decision-making task, high-density electrophysiology, and computational modeling. GC population dynamics represented stimuli linearly during taste sampling and choices categorically before decisions. Single neurons were classified by their linear and categorical activity patterns, revealing subpopulations encoding sensory, perceptual, and decisional variables. To test their functional role, we built a recurrent neural network model of GC. Model perturbations showed linear and categorical neurons were essential for driving normal population dynamics and behavioral performance, whereas many units with other activity patterns could be silenced without consequence. These results have implications that extend beyond GC, and demonstrate the role of linear and categorical coding neurons in cortical dynamics and behavior during perceptual decision-making.

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bioRxiv2024

Modulation of sweet preference by neurosteroid-sensitive, δ-GABAA receptors in adult mouse gustatory insular cortex

Taste preference is a fundamental driver of feeding behavior influencing dietary choices and eating patterns. Extensive experimental evidence indicates that the gustatory cortex (GC) is engaged in taste perception, palatability and preference. However, our knowledge of the neural and neurochemical signals regulating taste preference is rather limited. Neuromodulators can affect preferences, though their effects on neural circuits for taste are incompletely understood. Neurosteroids are of particular interest in view of reports that systemic administration of the neurosteroid allopregnanolone, a potent modulator of tonic GABAergic inhibition, induces hyperphagia and increases intake of energy rich food in human and animal subjects. Tonic inhibition is a powerful modulator of circuit excitability and is primarily mediated by extrasynaptic GABAA receptors containing the delta subunit ({delta}-GABAARs). These receptors are widely distributed in the brain, but information regarding the expression of {delta}-GABAARs within gustatory circuits is lacking, and their role in taste preference has not been investigated. Here, we focused on GC to investigate whether activation of {delta}-GABAARs affects sweet taste preference in adult mice. Our data reveal that {delta}-GABAARs are expressed in multiple cell types within GC. These receptors mediate an allopregnanolone-sensitive tonic current and decrease sweet taste preference by altering the behavioral sensitivity to sucrose concentration in a cell type-specific manner. Our findings demonstrate that taste sensitivity and preference in the adult mammalian brain are modulated by tonic inhibition mediated by neurosteroid-activated {delta}-GABAARs in GC.

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bioRxiv2023

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.

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bioRxiv2022

Inhibitory gating of thalamocortical inputs onto rat gustatory insular cortex

In the rat primary gustatory cortex (GC), a subregion of the larger insular cortex, neurons display time-varying neural responses to gustatory stimuli. GC taste responses are dramatically reduced following inactivation of the gustatory thalamus, the parvicellular region of the ventral posteromedial thalamic nucleus (VPMpc). Pharmacological inactivation of VPMpc also has a profound effect on GC spontaneous activity. This indicates that the projection from VPMpc plays a crucial role in GC taste processing as well as in the control of its state. How VPMpc afferents engage GC circuits and drive neuronal ensembles to effectively code tastant identity, as well as modulate the overall state of the GC network, remains unclear. To investigate the synaptic properties and organization of VPMpc afferents in GC, we employed a circuit-breaking optogenetic approach, stimulating VPMpc terminal fields while performing whole-cell patch clamp recordings from GC neurons in rat acute slices. Informed by previous studies of thalamocortical inputs to other sensory cortices, we hypothesized that VPMpc-GC synapses have laminar- and cell-specific properties that gate sensory input, conferring computationally flexibility to how taste information is processed in GC. We found that VPMpc-GC synapses are strongly gated by the activity regime of VPMpc afferents, as well as by feedforward and feedback inhibition onto VPMpc terminals. These results provide novel insight into the circuit underpinning of GC responsiveness to incoming thalamocortical activity. SIGNIFICANCE STATEMENTWe report that the input from the primary taste thalamus to the primary gustatory cortex (GC) shows distinct properties compared to primary thalamocortical synapses onto other sensory areas. VPMpc 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. Feedforward inhibition gates thalamocortical activation and provides local corticothalamic feedback via presynaptic ionotropic and metabotropic GABA receptors. The connectivity and inhibitory control of thalamocortical synapses support the time-varying response dynamics to taste stimuli observed in GC neurons in vivo.

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bioRxiv2022

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 tastants 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 experience in setting taste preferences.

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bioRxiv2022

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 models 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.

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bioRxiv2020

Spatially distributed representation of taste quality in the gustatory insular cortex of awake 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.

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bioRxiv2019

Dynamic representation of taste-related decisions in the gustatory insular cortex of mice

Research over the past decade has established the gustatory insular cortex (GC) as a model for studying how primary sensory cortices integrate multiple sensory, affective and cognitive signals. This integration occurs through time varying patterns of neural activity. Selective silencing of GC activity during specific temporal windows provided evidence for GCs role in mediating taste palatability and expectation. Recent results also suggest that this area may play a role in decision making. However, existing data are limited to GC involvement in controlling the timing of stereotyped, orofacial reactions to aversive tastants during consumption. Here we present electrophysiological, chemogenetic and optogenetic results demonstrating the key role of GC in the execution of a taste-guided, reward-directed decision making task. Mice were trained in a taste-based, two-alternative choice task, in which they had to associate tastants sampled from a central spout with different actions (i.e., licking either a left or a right spout). Stimulus sampling and action were separated by a delay period. Electrophysiological recordings of single units revealed chemosensory processing during the sampling period and the emergence of task-related, cognitive signals during the delay period. Chemogenetic silencing of GC impaired task performance. Optogenetic silencing of GC allowed us to tease apart the contribution of activity during the sampling and the delay periods. While silencing during the sampling period had no effect, silencing during the delay period significantly impacted behavioral performance, demonstrating the importance of the cognitive signals processed by GC during this temporal window in driving decision making. Altogether, our data highlight a novel role of GC in controlling taste-guided, reward-directed choices and actions.

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bioRxiv2019

LTD at amygdalocortical synapses as a novel mechanism for hedonic learning

A novel, pleasant taste stimulus becomes aversive if associated with gastric malaise, a form of learning known as conditioned taste aversion (CTA). CTA is common to vertebrates and invertebrates and is an important survival response: eating the wrong food may be deadly. CTA depends on the gustatory portion of the insular cortex (GC) and the basolateral nucleus of the amygdala (BLA) however, its synaptic underpinnings are unknown. Here we report that CTA was associated with decreased expression of immediate early genes in rat GC of both sexes, and with reduced amplitude of BLA-GC synaptic responses, pointing to long term depression (LTD) as a mechanism for learning. Indeed, association of a novel tastant with induction of LTD at the BLA-GC input in vivo was sufficient to change the hedonic value of a taste stimulus. Our results demonstrate a direct role for amygdalocortical LTD in taste aversion learning.

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bioRxiv2018

Disruption of cortical dopaminergic modulation delays licking initiation

Dysfunction of motor cortices is thought to contribute to motor disorders such as Parkinsons 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 mice with unilateral depletion of dopaminergic neurons (i.e., mice injected with 6-OHDA into the medial forebrain bundle). Hemi-lesioned 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 hemi-lesioned mice. Altogether, our data show a direct relationship between cortical D1 receptor modulation, cue-evoked and preparatory activity in ALM, and licking initiation.\n\nSIGNIFICANCE STATEMENTThe link between dopaminergic signaling, motor cortical activity and motor deficits is not fully understood. This manuscript describes alterations in neural activity of the anterior lateral motor cortex (ALM) that correlate with licking deficits in mice with unilateral dopamine depletion or with intra-ALM infusion of dopamine antagonist. The findings emphasize the importance of cortical dopaminergic modulation in motor initiation. These results will appeal not only to researchers interested in cortical control of licking, but also to a broader audience interested in motor control and dopaminergic modulation in physiological and pathological conditions. Specifically, our data suggest that dopamine deficiency in motor cortex could play a role in the pathogenesis of the motor symptoms of Parkinsons disease.

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bioRxiv2017

Expectation-induced modulation of metastable activity underlies faster coding of sensory stimuli

Sensory stimuli can be recognized more rapidly when they are expected. This phenomenon depends on expectation affecting the cortical processing of sensory information. However, virtually nothing is known on the mechanisms responsible for the effects of expectation on sensory networks. Here, we report a novel computational mechanism underlying the expectation-dependent acceleration of coding observed in the gustatory cortex (GC) of alert rats. We use a recurrent spiking network model with a clustered architecture capturing essential features of cortical activity, including the metastable activity observed in GC before and after gustatory stimulation. Relying both on network theory and computer simulations, we propose that expectation exerts its function by modulating the intrinsically generated dynamics preceding taste delivery. Our model, whose predictions are confirmed in the experimental data, demonstrates how the modulation of intrinsic metastable activity can shape sensory coding and mediate cognitive processes such as the expectation of relevant events. Altogether, these results provide a biologically plausible theory of expectation and ascribe a new functional role to intrinsically generated, metastable activity.

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