Biology subjects

Katz, D. B.

Publications and source records attributed to Katz, D. B..

17 recordsLinked to original sources

bioRxiv2025

The Ingestive Response Reflects Neural Dynamics in Gustatory Cortex

Upon delivery of a taste onto the tongue, gustatory neural activity determines whether the stimulus is ingested or rejected. While some work in rodents has been devoted to investigating the neural activity leading to the rejection decision and its associated orofacial movements, little is known about what behaviors lead to ingestion of palatable tastes (and what neural activity is associated with that decision), largely because identifying ingestion-related behaviors is a difficult challenge--and probably undoable with video analysis given that the behaviors are largely intraoral. To address this gap in our understanding, we analyzed simultaneously-collected electromyographic (EMG) activity of the jaw opener muscle and the firing of gustatory cortical (GC) ensembles. We developed a machine-learning classifier to identify individual orofacial movements from EMG signals, demonstrating that it outperforms previously developed methods and using the technique to reveal three novel subtypes of ingestion-related tongue/mouth movements. Investigating the dynamics of these behaviors, we found that the frequency of occurrence of each type subtype shifts significantly at the time of the consumption decision, and is both tightly coupled with and reliably follows the transition in GC population activity into the state reflecting the tastants emotional/hedonic value. However, rather than the onset of single "ingestion" movement (as occurs for rejection decisions in the form of gapes), we show that the transition to ingestion is instead characterized by a collective change in the frequencies all ingestion-related behaviors. These findings demonstrate a direct link between neural dynamics in GC and the orchestration of the physical movements that define ingestive behavior, highlighting GCs general role in taste perception, decision making, and the control of motor actions.

neuroscience↗

bioRxiv2025

Perceptual processing of tastes is performed by the amygdala-cortical loop

Gustatory cortical (GC) and basolateral amygdalar (BLA) taste responses consist of an inter-regionally coherent 3-part state sequence. This coherence suggests that reciprocal BLA-GC connectivity is important for taste processing, but it remains unknown: 1) whether BLA-GC coherence actually reflects a reciprocal "conversation" (as opposed to one region simply driving the other); and 2) whether such a "conversation" has anything to do with the taste processing observed within GC response dynamics. Here, we address these questions using network and single-neuron analysis of simultaneously-recorded GC and BLA taste responses in awake rats. We find asymmetric, reciprocal {micro}-frequency influences that reflect taste processing dynamics: BLA[->]GC influence dominates between 300 and 1000msec (the epoch in which BLA codes palatability); afterward, when GC responses become palatability-related and GC has been shown to release a behavior-relevant signal, the direction of influence reverses, becoming GC[->]BLA. Follow-up analyses demonstrate that this "turn-taking" exists alongside effectively synchronous amygdala-cortical coupling--the two regions functioning as a unified structure. Finally, to assess the implications of these interactions for single-neuron responses, we tested the response properties of GC neurons categorized by their inferred connectivity with BLA: GC neurons influenced by BLA produce stronger taste-specific and palatability-related responses than other GC neurons, and the strongest taste encoding is specifically found in GC neurons that both influence and receive influence from BLA--those most deeply embedded in the reciprocal circuit. These results, consistent with findings in multiple systems, support the novel conclusion that taste processing and decision-making is a function of the amygdala-cortical loop. New & NoteworthyConventionally, taste circuitry is considered feedforward, travelling up from the brainstem, with each additional node containing more sophisticated information. We challenge this convention by demonstrating that amygdala and cortex instead influence each other bidirectionally, yet in a direction-specific and asymmetric manner. These influences appear to drive different parts of the taste response, with distinct patterns for decision-making and behavioral output; furthermore, involvement in cortex-amygdala functional connectivity determines the strength of encoding in cortical single neurons.

neuroscience↗

bioRxiv2024

Neural correlates of rapid familiarization to novel taste

The gustatory cortex (GC) plays a pivotal role in taste perception, with neural ensemble responses reflecting taste quality and influencing behavior. Recent work, however, has shown that GC taste responses change across sessions of novel taste exposure in taste-naive rats. Here, we use single-trial analyses to explore changes in the cortical taste-code on the scale of individual trials. Contrary to the traditional view of taste perception as innate, our findings suggest rapid, experience-dependent changes in GC responses during initial taste exposure trials. Specifically, we find that early responses to novel taste are less "stereotyped" and encode taste identity less reliably compared to later responses. These changes underscore the dynamic nature of sensory processing and provides novel insights into the real-time dynamics of sensory processing across novel-taste familiarization.

neuroscience↗

bioRxiv2024

Changes in taste palatability across the estrous cycle are modulated by hypothalamic estradiol signaling

Food intake varies across the stages of a rats estrous cycle. It is reasonable to hypothesize that this cyclic fluctuation in consumption reflects an impact of hormones on taste palatability/preference, but evidence for this hypothesis has been mixed, and critical within-subject experiments in which rats sample multiple tastes during each of the four main estrous phases (metestrus, diestrus, proestrus, and estrus) have been scarce. Here, we assayed licking for pleasant (sucrose, NaCl, saccharin) and aversive (quinine-HCl, citric acid) tastes each day for 5-10 days while tracking rats estrous cycles through vaginal cytology. Initial analyses confirmed the previously-described increased consumption of pleasant stimuli 24-48 hours following the time of high estradiol. A closer look, however, revealed this effect to reflect a general magnification of palatability--higher than normal preferences for pleasant tastes and lower than normal preferences for aversive tastes--during metestrus. We hypothesized that this phenomenon might be related to estradiol processing in the lateral hypothalamus (LH), and tested this hypothesis by inhibiting LH estrogen receptor activity with ICI182,780 during tasting. Control infusions replicated the metestrus magnification of palatability pattern; ICI infusions blocked this effect as predicted, but failed to render preferences "cycle free," instead delaying the palatability magnification until diestrus. Clearly, estrous phase mediates details of taste palatability in a manner involving hypothalamic actions of estradiol; further work will be needed to explain the lack of a flat response across the cycle with hypothalamic estradiol binding inhibited, a result which perhaps suggests dynamic interplay between brain regions or hormones. Significance StatementConsummatory behaviors are impacted by many variables, including naturally circulating hormones. While it is clear that consumption is particularly high during the stages following the high-estradiol stage of the rodents estrous (and human menstrual) cycle, it is as of yet unclear whether this phenomenon reflects cycle stage-specific palatability (i.e., whether pleasant tastes are particularly delicious, and aversive tastes particularly disgusting, at particular phases). Here we show that palatability is indeed modulated by estrous phase, and that this effect is governed, at least in part, by the action of estradiol within the lateral hypothalamus. These findings shed light on the mechanisms underlying the adverse impact on human welfare due to irregularities observed across the otherwise cyclic menstrual process.

neuroscience↗

bioRxiv2024

Experience-induced drift in the neural coding of individual differences in perception

As is true in humans, no two rodents prefer precisely the same tastes. Furthermore, no one rodent keeps precisely the same taste preferences forever. Here, we have made use of this between- and within-animal variability to generate and test novel hypotheses about the stability and malleability of neural perceptual coding. We used a brief-access task (BAT) to reveal both individual differences in taste preferences and shifting preferences within individual rats (quantified in terms of lick bout lengths). We moved on to show that these phenomena are not simply random variation: first, by demonstrating that gustatory cortical (GC) taste response dynamics, the late part of which reflect palatability, match that individual rat's BAT preferences (evaluated almost 2 weeks prior) better than canonical preference patterns; that is, individual differences in preferences reflect differences in neural taste processing. This match, however, links neural taste processing only to the most recent BAT session--GC palatability processing does not reflect performance in earlier BAT sessions. We hypothesized that any tasting experience might impact taste processing (i.e., not just BAT licking), and tested this hypothesis by adding a second session of GC taste-response recordings; palatability-epoch taste responses in this later session no longer matched the most recent pre-recording BAT session, demonstrating that responses following the first electrophysiology session had changed. Together, these data demonstrate that every tasting experience (regardless of the method of taste delivery) changes the rat's processing of those tastes.

neuroscience↗

bioRxiv2021

Impact of hedonic value of stimuli on sampling dynamics during a preference test

Food or taste preference tests are analogous to naturalistic decisions in which the animal selects which stimuli to sample and for how long to sample them. The data acquired in such tests, the relative amounts of the alternative stimuli that are sampled and consumed, indicate the preference for each. While such preferences are typically recorded as a single quantity, an analysis of the ongoing sampling dynamics producing the preference can reveal otherwise hidden aspects of the decision-making process that depend on its underlying neural circuit mechanisms. Here, we perform a dynamic analysis of two factors that give rise to preferences in a two-alternative task, namely the distribution of durations of sampling bouts of each stimulus and the likelihood of returning to the same stimulus or switching to the alternative--i. e., the transition probability--following each bout. The results of our analysis support a specific computational model of decision-making whereby an exponential distribution of bout durations has a mean that is positively correlated with the palatability of that stimulus, but also negatively correlated with the palatability of the alternative. This impact of the alternative stimulus on the distribution of bout durations decays over a timescale of tens of seconds, even though the memory of the alternative stimulus lasts far longer--long enough to impact the transition probabilities upon ending bouts. Together, our findings support a state-transition model for bout durations and suggest a separate memory mechanism for stimulus-selection.

animal behavior and cognition↗

bioRxiv2021

Loss of Stk11 in basolateral amygdalar projection neurons impairs CTA learning by altering the temporal pattern of taste response plasticity in GC

Gustatory cortex (GC) responds to tastes on the tongue with dynamic ensemble activity that represents first the presence, then the identity, and finally the hedonic value (palatability) of tastes. This final state of the taste response is uniquely altered by conditioned taste aversion (CTA) - a powerful one-trial learning paradigm in which a taste becomes aversive after association with gastric malaise - a process requiring coordination between GC and basolateral amygdala (BLA). Previously, we found that one key requirement for learning in this circuit is expression of the serine/threonine kinase 11 (Stk11) gene (a tumor suppression gene which has only recently been associated with learning; Levitan et al., 2020). When Stk11 is knocked out in BLA projection neurons (BLApn), CTA learning fails to occur. Here we have examined how learning-related response plasticity in GC taste responses is impacted by the knockout of Stk11 in BLApn. Contrary to the commonly held assumption that a lack of learning means a lack of such plasticity, but consistent with the fact that Stk11KO has been shown to increase the excitability of BLApn, our data reveal that the knockout of Stk11 in BLApn does not eliminate plasticity; rather, it shifts the impact of CTA training on GC taste responses to an earlier, learning-inappropriate epoch. Even naive taste representations are altered--specifically, the pattern of similarities and differences among the different taste responses are rendered abnormal by Stk11 KO, and these relationships fail to change with training. Finally, the latency of behavior-related dynamic ensemble features of the GC taste response, which is also abnormal in naive KO mice, is rendered disorganized by CTA. Together, these results suggest that Stk11 plays a role in governing the coordination of GC activity by BLA, and demonstrate that alterations in the function of BLApn caused by Stk11KO inhibit learning not by inhibiting plasticity but by changing its temporal properties.

neuroscience↗

bioRxiv2021

A model of naturalistic decision making in preference tests

Decisions as to whether to continue with an ongoing activity or to switch to an alternative are a constant in an animals natural world, and in particular underlie foraging behavior and performance in food preference tests. Stimuli experienced by the animal both impact the choice and are themselves impacted by the choice, in a dynamic back and forth. Here, we present model neural circuits, based on spiking neurons, in which the choice to switch away from ongoing behavior instantiates this back and forth, arising as a state transition in neural activity. We analyze two classes of circuit, which differ in whether state transitions result from a loss of hedonic input from the stimulus (an "entice to stay" model) or from aversive stimulus input (a "repel to leave" model). In both classes of model, we find that the mean time spent sampling a stimulus decreases with increasing value of the alternative stimulus, a fact that we linked to the inclusion of depressing synapses in our model. The competitive interaction is much greater in "entice to stay" model networks, which has qualitative features of the marginal value theorem, and thereby provides a framework for optimal foraging behavior. We offer suggestions as to how our models could be discriminatively tested through the analysis of electrophysiological and behavioral data. Author summaryMany decisions are of the ilk of whether to continue sampling a stimulus or to switch to an alternative, a key feature of foraging behavior. We produce two classes of model for such stay-switch decisions, which differ in how decisions to switch stimuli can arise. In an "entice-to-stay" model, a reduction in the necessary positive stimulus input causes switching decisions. In a "repel-to-leave" model, a rise in aversive stimulus input produces a switch decision. We find that in tasks where the sampling of one stimulus follows another, adaptive biological processes arising from a highly hedonic stimulus can reduce the time spent at the following stimulus, by up to ten-fold in the "entice-to-stay" models. Along with potentially observable behavioral differences that could distinguish the classes of networks, we also found signatures in neural activity, such as oscillation of neural firing rates and a rapid change in rates preceding the time of choice to leave a stimulus. In summary, our model findings lead to testable predictions and suggest a neural circuit-based framework for explaining foraging choices.

neuroscience↗

bioRxiv2020

Homeostatic Synaptic Scaling Establishes the Specificity of an Associative Memory

Accurate memory formation has been hypothesized to depend on both rapid Hebbian plasticity for initial encoding, and slower homeostatic mechanisms that prevent runaway excitation and subsequent loss of memory specificity. Here, we tested the role of synaptic scaling in shaping the specificity of conditioned taste aversion (CTA) memory, a Hebbian plasticity-dependent form of associative learning. We found that CTA memory initially generalized to non-conditioned tastants (generalized aversion), becoming specific to the conditioned tastant only over the course of many hours. Blocking synaptic scaling in the gustatory cortex (GC) prolonged the duration of the initial generalized aversion and enhanced the persistence of synaptic strength increases observed after CTA. Taken together, these findings demonstrate that synaptic scaling is important for sculpting the specificity of an associative memory and suggest that the relative strengths of Hebbian and homeostatic plasticity can modulate the balance between stable memory formation and generalization.

neuroscience↗

bioRxiv2020

Perturbation of amygdala-cortical projections reduces ensemble coherence of palatability coding in gustatory cortex

Taste palatability is centrally involved in consumption decisions--we ingest foods that taste good and reject those that dont. Gustatory cortex (GC) and basolateral amygdala (BLA) almost certainly work together to mediate palatability-driven behavior, but the precise nature of their interplay during taste decision-making is still unknown. To probe this issue, we discretely perturbed (with optogenetics) activity in BLA[->]GC axons during taste deliveries. This perturbation strongly altered GC taste responses, but while the perturbation itself was tonic (2s), the alterations were not--changes preferentially aligned with the onset times of previously-described taste response epochs, and reduced evidence of palatability-related activity in the "late-epoch" of the responses without reducing the amount of taste identity information available in the "middle epoch." Finally, BLA[->]GC perturbations changed behavior-linked taste response dynamics themselves, distinctively diminishing the abruptness of ensemble transitions into the late epoch. These results suggest that BLA "organizes" behavior-related GC taste dynamics.

neuroscience↗

bioRxiv2019

Single Cell RNA Sequencing Reveals Heterogeneity of Human MSC Chondrogenesis: Lasso Regularized Logistic Regression to Identify Gene and Regulatory Signatures

Bone marrow-derived mesenchymal stem cells (MSCs) exhibit the potential to undergo chondrogenesis in vitro, forming de novo tissues with a cartilage-like extracellular matrix that is rich in glycosaminoglycan and collagen type II. However, it is now apparent that MSCs comprise an inhomogeneous population of cells, and the fate of individual subpopulations during this differentiation process is not well understood. We analyzed the trajectory of MSC differentiation during chondrogenesis using single cell RNA sequencing (scRNA-seq). Using a machine learning technique - lasso regularized logistic regression - we showed that multiple subpopulations of cells existed at all stages during MSC chondrogenesis and were better-defined by transcription factor activity rather than gene expression. Trajectory analysis indicated that subpopulations of MSCs were not intrinsically specified or restricted, but instead remained multipotent and could differentiate into three main cell types: cartilage, hypertrophic cartilage, and bone. Lasso regularized logistic regression showed several advances in scRNA-seq analysis, namely identification of a small number of highly influential genes or transcription factors for downstream validation, and cell type classification with high accuracy. Additionally, we showed that MSC differentiation trajectory may exhibit donor to donor variation, although key influential pathways were comparable between donors. Our data provide an important resource to study gene expression and to deconstruct gene regulatory networks in MSC differentiation.

genomics↗

bioRxiv2019

Deletion of Stk11 and Fos in BLA projection neurons alters their intrinsic excitability and impairs formation of long-term aversive memory

Conditioned taste aversion (CTA) is a form of one-trial learning dependent on basolateral amygdala projection neurons (BLApn). Its underlying cellular and molecular mechanisms are poorly understood, however. We used RNAseq from BLApn to identify learning-related changes in Stk11, a kinase with well-studied roles in growth, metabolism and development, but not previously implicated in learning. Deletion of Stk11 restricted to BLApn completely blocks memory when occurring prior to training, but not following it, despite altering neither BLApn-dependent encoding of taste palatability in gustatory cortex, nor transcriptional activation of BLApn during training. Deletion of Stk11 in BLApn also increases their intrinsic excitability. Conversely, BLApn activated by CTA to express the immediate early gene Fos had reduced excitability. BLApn knockout of Fos also increased excitability and impaired learning. These data suggest that Stk11 and Fos expression play key roles in CTA long-term memory formation, perhaps by modulating the intrinsic excitability of BLApn.

neuroscience↗

bioRxiv2019

Reorganization and reactivation of a preexisting taste-responsive hippocampal network

Animals need to remember the locations of nourishing and toxic food sources for survival, a fact that necessitates a mechanism for associating taste experiences with particular places. We have previously identified such responses within hippocampal place cells [1], the activity of which is thought to aid memory-guided behavior by forming a mental map of an animals environment that can be reshaped through experience [2-7]. It remains unknown, however, whether taste-responsiveness is intrinsic to a subset of place cells, or emerges as a result of experience that reorganizes spatial maps. Here, we recorded from neurons in the dorsal CA1 region of rats running for palatable tastes delivered via intra-oral cannulae at specific locations on a linear track. We identified a subset of taste-responsive cells that, even prior to taste exposure, had larger place fields than non-taste-responsive cells overlapping with stimulus delivery zones. Taste-responsive cells place fields then contracted, as a result of taste experience, leading to a stronger representation of stimulus delivery zones on the track. Taste-responsive units exhibited increased sharp-wave ripple co-activation during the taste delivery session and subsequent rest periods, which correlated with the degree of place field contraction. Our results reveal that novel taste experience evokes responses within a preconfigured network of taste-responsive hippocampal place cells with large fields, whose spatial representations are refined by sensory experience to signal areas of behavioral salience. This represents a possible mechanism by which animals identify and remember locations where ecologically relevant stimuli are found within their environment.

neuroscience↗

bioRxiv2019

Single and population coding of taste in the gustatory cortex of awake mice

Electrophysiological analysis has reveals much about the broad coding and neural ensemble dynamics that characterize gustatory cortical (GC) taste processing in awake rats, and about how these dynamics relate to behavior. With regard to mice, meanwhile, data concerning cortical taste coding have largely been restricted to imaging--a technique that reveals average levels of neural responsiveness, but that (currently) lacks the temporal sensitivity necessary for evaluation of fast response dynamics; furthermore, the few extant studies have thus far failed to provide consensus on basic features of coding. We have recorded the spiking activity of ensembles of GC neurons while presenting representatives of the basic taste modalities (sweet, salty, sour and bitter) to awake mice. Our first central result is the identification of similarities between rat and mouse taste processing: most mouse GC neurons (~66%) responded distinctly to multiple (3-4) tastes; temporal coding analyses further reveal, for the first time, that single mouse GC neurons sequentially code taste identity and palatability--the latter responses emerging ~0.5s after the former--with whole GC ensembles transitioning suddenly and coherently from coding taste identity to coding taste palatability. The second finding is that spatial location plays very little role in any aspect of taste responses--neither between- (anterior-posterior) nor within-mouse (dorsal-ventral) mapping revealed anatomical regions with narrow or temporally simple taste responses. These data confirm recent results showing that mouse cortical taste responses are not \"gustatopic,\" but also go beyond these imaging results to show that mice process tastes through time.

neuroscience↗

bioRxiv2018

Dynamical structure of cortical taste responses revealed by precisely-timed optogenetic perturbation

The purpose of perception is driving action. During tasting, for instance, every stimulus must be either swallowed or rejected (the latter via a behavior known as "gaping"). Taste responses in the rodent primary gustatory cortex (GC) span this sensorimotor divide, progressing through a series of firing epochs that culminate in the emergence of action-related firing. Population analyses reveal this emergence to be a sudden, coherent ensemble transition that, despite varying in latency between trials, precedes gaping onset by 0.2-0.3s. Here, we tested whether this transition drives gaping, delivering 0.5s GC perturbations at various time-points in tasting trials. Perturbations significantly delayed gaping, but only when they preceded the action-related transition - thus, the same perturbation might have an impact or not, depending on the transition latency in that particular trial. Our results suggest a distributed attractor network model of taste processing, and a dynamical role for cortex in driving motor behavior.

neuroscience↗

bioRxiv2018

Interaction of taste and place coding in the hippocampus

An animals survival depends on finding food, and the memory of food and contexts are often linked. Given that the hippocampus is required for spatial and contextual memory, it is reasonable to expect related coding of space and food stimuli in hippocampal neurons. However, relatively little is known about how the hippocampus responds to tastes, the most central sensory property of food. In this study, we examined the taste-evoked responses and spatial firing properties of single units in the dorsal CA1 hippocampal region as male rats received a battery of taste stimuli differing in both chemical composition and palatability within a specific spatial context. We identified a subset of hippocampal neurons that responded to tastes, some of which were place cells. These taste and place responses had a distinct interaction: taste-responsive cells tended to have less spatially specific firing fields, and place cells only responded to tastes delivered inside their place field. Like neurons in the amygdala and lateral hypothalamus, hippocampal neurons discriminated between tastes predominantly on the basis of palatability, with taste-selectivity emerging concurrently with palatability-relatedness; these responses did not reflect movement or arousal. However, hippocampal taste responses emerged several hundred msec later than responses in other parts of the taste system, suggesting that the hippocampus does not influence real-time taste decisions, instead associating the hedonic value of tastes with a particular context. This incorporation of taste responses into existing hippocampal maps could be one way that animals use past experience to locate food sources.\n\nSignificance statementFinding food is essential for animals survival, and taste and context memory are often linked. While hippocampal responses to space and contexts have been well characterized, little is known about how the hippocampus responds to tastes. Here, we identified a subset of hippocampal neurons that discriminated between tastes based on palatability. Cells with stronger taste responses typically had weaker spatial responses, and taste responses were confined to place cells firing fields. Hippocampal taste responses emerged later than in other parts of the taste system, suggesting that the hippocampus does not influence taste decisions, but rather, associates the hedonic value of tastes consumed within a particular context. This could be one way that animals use past experience to locate food sources.

neuroscience↗

bioRxiv2018

The role of the gustatory cortex in incidental experience-evoked enhancement of later taste learning

The strength of learned associations between pairs of stimuli is affected by multiple factors, the most extensively studied of which is prior experience with the stimuli themselves. In contrast, little data is available regarding how experience with incidental stimuli (independent of any conditioning situation) impacts later learning. This lack of research is striking given the importance of incidental experience to survival. We have recently begun to fill this void using conditioned taste aversion (CTA), wherein an animal learns to avoid a taste that has been associated with malaise. We previously demonstrated that incidental exposure to salty and sour tastes (taste pre-exposure, TPE) enhances aversions learned later to sucrose. Here, we investigate the neurobiology underlying this phenomenon. First, we use immediate early gene (cFos) expression to identify gustatory cortex (GC) as a site at which TPE specifically increases the neural activation caused by taste-malaise pairing (i.e., TPE did not change cFos induced by either stimulus in isolation). Next, we use site-specific infection with the optical silencer Archaerhodopsin-T to show that GC inactivation during TPE inhibits the expected enhancements of both learning and CTA related cFos expression, a full day later. Thus, we conclude that GC is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning.

neuroscience↗