Learning dynamics depend on internal and contextual multifactors among which the interaction between motivational context and task demands play an important role. Spatial navigation provides a powerful framework to study these interactions as it integrates cognitive, motivational and motor components. To examine how reward modality and task complexity modulate learning dynamics in male mice, we used a sequential navigation task in which the number of decision points progressively increased across training, while preserving the same geometrical context and goal location. We compared three versions of the same task, in which the fixed goal location was rewarded by either escape from water (aquatic version), food pellets, or medial forebrain bundle (MFB) stimulation associated with different levels of complexity. At low task complexity, the aquatic group achieved a higher level of performance. However, this effect does not extend to the acquisition of the most complex sequence, as all groups ultimately converge toward comparable abilities to perform direct trials. Furthermore, reward type appears to modulate motivational engagement and speed in all training conditions. Together, these data show that, during spatial navigation, reward modality influences not only the level of learning but also its behavioral execution.Significance Statement Navigation relies on the interaction between cognitive demands and motivational context, yet their combined influence on learning dynamics remains poorly understood. Here, we compare how different reward modalities shape the acquisition of a sequential navigation task within a single, controlled environment, while systematically increasing task complexity. We show that reward modality strongly biases early strategy selection under low cognitive demand and continues to modulate learning acquisition as the number of successive choices increase. By isolating reward effects within the same behavioral structure, this work provides an insight to understand how motivation and task complexity jointly shape navigation strategies.
Electroencephalographic (EEG) studies of human quiet stance demonstrate beta-band event-related desynchronization (beta-ERD) during the micro-fall phase of postural sway, followed by event-related synchronization (beta-ERS; post-movement beta rebound) during the micro-recovery phase. These modulations correlate with intermittent ankle muscle inactivation that exploits the stable manifolds of an unstable upright equilibrium; however, how such sway-related beta dynamics may arise within closed-loop brain-body interactions remains unclear. Here, we investigated a possible circuit-level account of these dynamics using an embodied spiking neural network model of the cortico-basal ganglia-thalamic (CBGT) circuitry integrated with an inverted pendulum. In this closed-loop system, continuous sensory feedback is integrated into the striatum, while the motor cortex executes decisions via drift-diffusion-like population competition, where the decision time (DT) represents the intermittent control-off period. We demonstrate that simulated cortical LFPs exhibit characteristic sway-phase-locked beta-ERD and beta-ERS when corticostriatal synaptic weights are functionally balanced to implement intermittent control. Conversely, a forced-choice continuous-like regime that ceaselessly generates feedback torque fails to replicate these modulations, sustaining flat network states devoid of control-off periods (DT). Structural dissections show that, within the model, disrupting bidirectional thalamocortical loops or the GPe-STN circuit abolishes sway-phase-locked beta modulation, despite continuous sensory drive. Our findings provide a computational account linking sway-phase-locked beta activity to intermittent motor selection within the proposed CBGT framework. This closed-loop modeling framework offers a testable candidate account for how alterations in brain-body dynamics may jointly affect behavioral intermittency and beta-band modulation, with potential relevance to postural impairments in clinical conditions such as Parkinson's disease.Significance Statement Intermittent motor commands during quiet standing are accompanied by phase-specific cortical beta-band modulations, but how these neural dynamics may relate to intermittent postural control remains unclear. Here, using a closed-loop model integrating spiking cortico-basal ganglia-thalamic (CBGT) circuitry with body dynamics, we show that human-like beta modulations arise when the model implements intermittent control. Within the model, these modulations are abolished by disrupting thalamocortical or GPe-STN interactions and are absent in a forced-choice continuous-like regime. These findings provide a computational account linking intermittent postural control to sway-related beta dynamics and identify circuit interactions sufficient for their emergence within the proposed CBGT framework. The model offers testable predictions for investigating how brain-body interactions shape beta dynamics in healthy and impaired postural control.
Activity-dependent structural plasticity is essential for the growth and remodeling of synaptic connections. At the Drosophila melanogaster larval neuromuscular junction (NMJ), spaced stimulation induces the translation-dependent formation of ghost boutons (GBs), which are immature boutons that lack a corresponding postsynaptic structure. Calcium/calmodulin-dependent protein kinase II (CaMKII) has previously been implicated in GB formation and is locally translated at synapses, raising the possibility that activity-dependent CaMKII synthesis contributes to GB formation. We examined activity-induced synaptic outgrowth in female larvae using a spaced depolarization paradigm combined with genetic manipulations of the endogenous CaMKII locus. While whole-animal CaMKII null mutants exhibited fewer GBs after spaced depolarization, selective disruption of activity-dependent CaMKII synthesis by deletion of the CaMKII 3' untranslated region (3'UTR) in either presynaptic motor neurons or postsynaptic muscle cells had no effect on GB formation. Consistent with this, inhibition of the signaling pathways upstream of CaMKII synthesis also did not impair bouton outgrowth. Cell-specific deletion of the CaMKII coding region in presynaptic neurons also did not alter GB formation, but postsynaptic deletion significantly reduced it. These findings demonstrate that local synthesis of CaMKII is dispensable for activity-dependent ghost bouton formation. Instead, our results indicate that only steady-state CaMKII protein is necessary for this specific type of structural plasticity and identifies a new trans-synaptic function for postsynaptic CaMKII in GB formation. These findings distinguish the role of CaMKII protein from CaMKII synthesis and suggest that other locally translated proteins underlie the protein synthesis dependence of GB formation.Significance Statement Local protein synthesis is thought to support long-lasting forms of synaptic plasticity. At the Drosophila neuromuscular junction, CaMKII is synthesized during patterned stimulation, which also triggers CaMKII-dependent ghost bouton formation, suggesting CaMKII local synthesis might be involved in this form of structural plasticity. In contrast to this hypothesis, disrupting activity-dependent CaMKII translation in either presynaptic or postsynaptic cells had no effect on ghost bouton formation. Instead, loss of CaMKII protein in the whole animal blocked synaptic outgrowth, and loss of postsynaptic CaMKII protein reduced it. Our findings indicate that CaMKII protein function, but not local CaMKII synthesis, is involved in activity-dependent ghost bouton formation. Identifying the precise molecular players driving local translation-dependent remodeling remains a task for future research.
Cultured dissociated trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons are widely used to study peripheral sensory function, yet direct electrophysiological comparisons under identical experimental conditions remain limited. We compared intrinsic electrophysiological properties of mouse TG (mTG) and mouse DRG (mDRG) neurons using whole-cell patch-clamp electrophysiology from male mice. In addition to conventional comparisons of membrane properties, action potential waveform characteristics, and firing behavior, neurons were stratified by soma size and analyzed using principal component analysis (PCA) and Pearson correlation analyses to determine ganglia-specific electrophysiological signatures. mTG neurons exhibited enhanced stimulus-evoked excitability compared with mDRG neurons, characterized by shorter first-spike latency, increased repetitive firing, and greater action potential output despite similar resting membrane potential, rheobase, and input resistance. These differences were primarily driven by small-diameter neurons, which displayed increased rebound and repetitive firing, whereas differences in spontaneous activity were predominantly observed in large-diameter neurons. PCA revealed distinct clustering of TG and DRG neurons based on electrophysiological properties, while Pearson correlation analyses demonstrated tissue-specific relationships among electrophysiological parameters, particularly involving afterhyperpolarization, indicating that coordinated regulation of excitability differs between sensory ganglia. These findings demonstrate that TG and DRG neurons differ not only in individual electrophysiological properties but also in the coordinated organization of those properties. Together, these data provide a functional framework for understanding ganglion-specific regulation of peripheral sensory neuron excitability and establish a foundation for future mechanistic studies and the development of targeted therapies for peripheral pain disorders.Significance Statement Trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons are fundamental models for studying peripheral sensory physiology and pain mechanisms. Although previous studies have identified differences in their anatomy, central circuitry, and transcriptomic profiles, direct comparisons of their intrinsic electrophysiological properties under identical experimental conditions have been lacking. Here, we demonstrate that cultured dissociated TG and DRG neurons exhibit distinct excitability profiles, firing behaviors, and coordinated electrophysiological signatures. These findings establish a functional framework linking molecular diversity to neuronal function, provide an important reference for interpreting studies of peripheral sensory neurons, and may facilitate the identification of ganglion-specific therapeutic strategies for sensory diseases such as neuropathic pain.
Each barrel of the barrel cortex (BC) receives thalamic input primarily from a single whisker. Barrels then communicate through intracortical circuitry to integrate input from multiple whiskers and perform processing functions such as spatial filtering, motion sensing, and object localization. To investigate the circuits that enable barrels to communicate independently of extracortical and inter-areal influences we prepared slices of somatosensory cortex from mice of both sexes with a hybrid voltage sensor (hVOS) targeted to Scnn1a excitatory neurons in cortical layer 4 (L4). We then imaged voltage responses of this population of neurons to electrical stimulation. Imaging tracked activity initiated in L4 of one barrel spreading into layer 2/3 (L2/3) and then to L4 of neighboring barrels. AMPA receptor blockade eliminated this spread, suggesting that L4 signaling to neighboring barrels employs an L4→L2/3→L4 excitatory synaptic relay. Blocking AMPA receptors also enhanced some responses, revealing intra- and inter-barrel feedforward inhibition. Both coronal and sagittal slices presented the layout of barrels, which aligned with facial whisker organization. We assessed inter-barrel communication in different directions and found it to be isotropic in response amplitude, half-width, and conduction velocity. However, latency was longest for communication to caudal barrels. Furthermore, paired-pulse depression was strongest and recovery slowest for inter-barrel communication related to exploratory protraction. Such biases have the potential to contribute to direction-sensitive processing. Anisotropy in short-term plasticity can tune BC microcircuits to preserve temporal fidelity and filter selectively according to direction.Significance Statement Sensory processing of spatiotemporal whisking patterns by the barrel cortex depends on complex interactions within the cortex and with extracortical areas. How intracortical circuits contribute to this processing is not well understood. Cell-type-specific voltage imaging in anatomically aligned slices of somatosensory cortex enabled the investigation of how barrels communicate. We identified a layer-specific synaptic circuit that mediates communication between barrels. Response latency and short-term synaptic depression of this inter-barrel relay vary with propagation direction. This direction dependence suggests that intracortical communication is tailored to the processing of natural whisker motion. By linking synaptic properties and circuit connectivity between barrels to anatomically aligned whisker architecture, this work advances our understanding of how neocortical networks process sensory input.
Ambient luminance varies widely, and retinal output is shaped by adaptation-dependent gain control. Relative to the adaptation level, a decrease in light intensity can either return intensity toward the adaptation level or drive it farther away from that level. Whether OFF retinal outputs signal both changes simply as light-intensity decrements or distinguish them according to their relationship to the adaptation level is currently unclear. This study examined OFF sustained retinal ganglion cells in bullfrogs ( Rana catesbeiana ) of either sex and quantified response bias by comparing spike counts during decrements that moved toward and away from the adaptation level. Responses fell into two functional populations: one signaled decrements in both cases, whereas the other selectively signaled decrements that moved away from the adaptation level, indicating adaptation level-referenced encoding. Although surround suppression was considered a possible contributor to these differences, manipulations expected to reduce classical surround contributions did not explain the selective suppression of responses during decrements that moved toward the adaptation level. Blocking GABA A receptors (GABA A Rs) consistently weakened the response asymmetry between decrements that moved toward and away from the adaptation level, suggesting that GABA A R-dependent inhibition contributes to the mechanism underlying adaptation level-referenced responses. Taken together, these findings reveal a distinct computation for light-intensity decrement processing and expand the functional diversity of OFF outputs across light-intensity contexts. Significance statement This study reveals functional diversity among OFF sustained retinal ganglion cells (RGCs) in frogs in how they encode light-intensity decrements relative to the adaptation level. Rather than simply reporting decrements, cells fell into two functional groups: one responded to decrements that moved toward and away from the adaptation level, whereas the other selectively responded to decrements that moved away from the adaptation level. This distinction indicates that these OFF-retinal outputs encode light-intensity decrements according to their relationship to the current visual context. These findings identify adaptation level-referenced responses in OFF sustained RGCs as a previously unrecognized form of OFF pathway processing.
Visual scene analysis relies on a set of scene-selective regions in the posterior cerebral cortex (OPA, PPA, MPA), with a paired memory-responsive counterpart located in the anterior (LPMA, VPMA) or overlapping (MPMA) cortex. The interaction between these pairs of regions is thought to integrate visual input with mnemonic context. Recently, a fourth scene perception area in the superior parietal cortex (the superior place area, SPA) was identified, with a proposed role in visually guided navigation. Whether this region also has an anterior paired memory region is currently unknown. Across two independent fMRI datasets (total N = 24, 14 females) using static or dynamic stimuli and distinct memory tasks, we show that recalling visual scenes evokes robust responses in a region immediately anterior and dorsal to SPA (referred to here as the superior place memory area, SPMA). During resting-state fMRI, SPA preferentially coupled with the other scene perception areas, while SPMA preferentially coupled with the other place memory areas. At the whole-brain level, seed-based connectivity revealed that SPA sits at the confluence of four processing streams spanning regions implicated in egocentric scene perception, map-based navigation, perspective taking, and goal-directed movement. These findings extend the perception-memory motif associated with visual scene processing to a fourth cortical surface. The widespread anatomical coupling between scene perception and memory processes reflects the importance of this interaction for flexible, context-grounded navigation.
Vagal sensory neurons play a central role in monitoring internal organ physiology and maintaining homeostasis. Although now recognized as key mediators of brain-body communication and promising therapeutic targets, their characterization emerged gradually over centuries of anatomical and microscopic investigation. This review provides a focused historical perspective on the study of vagal sensory neurons, emphasizing morphological and histological developments prior to the molecular era. Drawing on a collection of images from historical literature, this article traces the evolution of ideas and techniques, highlighting how early anatomical and histological studies established the foundation for modern investigations into vagal sensory function in health and disease. The review features the contributions of both well-known pioneers, including Adolph Hannover, Albert von Kölliker, Santiago Ramón y Cajal, and Fernando de Castro, as well as lesser-known investigators such as Adam Ploschko, Sergey Izhevesky, and Margaret Brown, whose work helped advance the field but has received comparatively little historical attention.
Chronic stress exposure causes neurobiological and behavioral changes that resemble those reported in psychiatric conditions such as major depressive disorder (MDD). Preclinical stress models and studies using postmortem tissue from MDD patients have shown that DNA damage-inducible transcript 4 (Ddit4) is increased in the prefrontal cortex (PFC). This is important because DDIT4 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which may lead to behavioral deficits through diminished neuroplasticity and PFC function. Our prior studies indicate that coordinated neuron-microglia interactions contribute to synaptic remodeling in the PFC. The present studies aimed to test the hypothesis that increased neuronal Ddit4 expression is sufficient to drive structural remodeling of PFC neurons, in part by provoking microglia activation, and this leads to behavioral and cognitive deficits. To this end, we bilaterally infused AAV5-hSyn1-Ddit4-tdTomato or a control vector into the PFC of male Thy1-GFP and C57BL/6 mice and examined molecular, cellular, and behavioral endpoints. Mice with Ddit4 overexpression (Ddit4-OV) showed no change in passive stress coping, yet exhibited deficits in temporal order memory. Immunohistology analyses showed a decrease in dendritic spine density of Ddit4-OV mice. However, we found no changes in microglia count, microglia size, or nearest neighbor distance. Bulk RNA sequencing of Ddit4-OV PFC revealed increases in transcripts involved with dendrite and synapse function and decreases in transcripts involved with mitochondrial function, implicating mTOR dysregulation. Altogether, these results indicate that Ddit4 overexpression recapitulates some of the broad molecular, cellular, and behavioral adaptations observed following chronic stress exposure through a cell-autonomous mechanism.
Animals produce different vocalization types, which differ in their acoustic features and are produced in different behavioral contexts. How vocalization-related brain circuits are organized to enable the production of different vocalization types remains poorly understood. The nucleus retroambiguus (RAm) is a hindbrain premotor region that regulates the production of both ultrasonic vocalizations (USVs) and distress calls (squeaks) in adult mice, but whether distinct or overlapping populations of RAm neurons are recruited during the production of these two vocalization types is unknown. In the current study, we used Fos immunohistochemistry to compare the counts and spatial distributions of Fos-positive RAm neurons in males and females that produced USVs and females that produced courtship squeaks. We also combined in vivo activity-dependent (TRAP2) labeling with Fos immunohistochemistry to directly compare Fos expression associated with the production of USVs and courtship squeaks in the same females. Our findings suggest that RAm contains three vocalization-related populations of neurons: squeak-related neurons, USV-related neurons, and shared neurons that are recruited during both vocalization types. These findings refine current models of the premotor control of vocalization and set the stage for future work to explore anatomical and functional heterogeneity within RAm.
The auditory brainstem plays a crucial role in speech-in-noise listening, refining numerous acoustic features such as pitch and spatial location under continual descending influence from cortex. However, the difficulty of characterizing brainstem activity during continuous speech listening has obscured its functional role in ecologically valid contexts-not only the effects of selective attention on neural responses, but also their impact on comprehension and listening effort. Here, we evaluated the role of the brainstem on speech-in-noise perception and other listening behaviors using a continuous, speech-based stimulus with embedded chirps (Cheech) that rapidly and effectively evoked auditory brainstem responses (ABRs) while 25 participants listened to short story narratives (n=15 females, 10 males). The Cheech-modified stories were presented alone or in the presence of another spatially separated talker, and neural responses were measured throughout by EEG. Both word-level detection performance and narrative-level comprehension were evaluated, as well as subjective reports of listening effort. ABR wave V was modulated by the presence of a competing talker. Additionally, wave V peak amplitudes were associated with identification speed of the target words embedded within the stories, while faster latencies related to better target word identification accuracy, comprehension question accuracy, and lower subjective listening effort. Collectively, our results provide evidence for the influence of brainstem encoding processes on individual speech-listening behaviors, including the ability to selectively attend to and comprehend target speech in the presence of a competing talker.Significance statement This study highlights the crucial role of the brainstem in speech-in-noise perception and higher-level language abilities like comprehension and subjective listening effort. Through the use of a novel speech stimulus blended with embedded chirps (Cheech) to evoke brainstem responses while listening to short story narratives, we show how subcortical processes relate to successful speech-listening performance across multiple behavioral metrics. These findings advance our understanding of how the brainstem supports speech perception, comprehension, and perceived effort in challenging listening environments.
Stress is a major risk factor for various psychiatric disorders. Activation of the hypothalamic-pituitary-adrenal axis increases cortisol release, whereas prolonged glucocorticoid exposure has been linked to cognitive impairment and mood disorders. In this study, we examined whether chronic corticosterone administration alters emotional states, active coping strategies, and associated neuronal activation in rats. Male Long-Evans rats were trained in a lever-press task to avoid signaled footshocks and then assigned into control or corticosterone-treated groups, with the latter receiving daily corticosterone injections for 21 consecutive days. Afterward, emotional states were assessed using the elevated plus maze (EPM), forced swim test (FST), and sucrose preference test (SPT). Finally, the animals were retested for their active avoidance behavior, while neuronal activation levels in related brain areas were evaluated. Our results showed that chronic corticosterone administration led to decrease in body weight and deteriorated fur condition over time. The stressed rats showed hypolocomotion in EPM but no changes in anxiety-like behavior, increased despair-like behavior in FST, and developed anhedonia in SPT. Despite these emotional alterations, active avoidance performance and freezing behavior were not affected. Consistently, analyses of numbers of c-Fos-positive neurons in the prelimbic cortex, infralimbic cortex, nucleus accumbens core, nucleus accumbens shell, dorsal CA3, and basolateral amygdala did not differ between groups. Together, our results suggested that chronic corticosterone administration induced physical deterioration. These animals were less active and developed behavioral despair and anhedonia, but did not alter their coping strategies to threat-related signals.
Male zebra finches begin their song bouts by repeating a short sound called an introductory note (IN). As INs repeat, their timing and acoustic properties change, similar to premovement neural preparatory activity seen in primates and rodents. Hence, INs are thought to reflect motor preparation for starting song. However, INs themselves are vocalizations/movements, like the song that follows, suggesting that INs could be part of the song sequence. To determine how similar songs and INs are, we compared their properties in adult, male zebra finches recorded across 3 years. First, song and INs simultaneously changed in the first year post-hatch; as described earlier, songs became faster and we found an increase of 0.58 ± 0.07 in mean IN number. Second, as described earlier, IN properties changed from first to last IN. Here, we found that these changes were driven by the last IN becoming more like the first song syllable in duration, amplitude, and timing. Third, within each bout, first song syllable timing was correlated with last IN timing in only 18% of birds. Amplitude and mean frequency of the first song syllable was correlated not only with the last IN, but also with the first IN and second song syllable in >40% of birds. Finally, the reduction in gaps between successive INs was not seen in other types of repeat syllables. Overall, the acoustic similarities between INs and song suggest that INs are part of the song sequence, but timing differences suggest different mechanisms for controlling IN timing.
Cognitive functioning depends on the brain's ability to process sensory information and simultaneously integrate contextual feedback from higher-order regions like the prefrontal cortex (PFC). This requires the sensory cortex (SC) to handle both processes simultaneously. Some phase-coupled oscillator models propose that the scaffolding of neuronal communication occurs via oscillatory coupling of low-frequency oscillations. However, it is often neglected that processing this bidirectional input poses serious temporal constraints on the system. Specifically, is it possible for SC to be coupled to PFC, while at the same time being coupled to the sensory input? In this article, we describe the temporal constraints required to simultaneously process feedforward and feedback information through oscillatory coupling. We adopt a dynamical systems perspective to suggest mechanisms by which phase-coupled oscillator models can achieve optimal temporal dynamics for neural communication while accounting for these temporal constraints. Although initially counterintuitive, our proposed framework indicates that any viable solution of bidirectional phase-based coupling inherently relies on the feedforward scaffolding of neuronal communication. The mechanisms proposed here may generalize to other situations in which brain areas need to cope with bidirectional feedforward and feedback interactions while maintaining phase coupling.
Persistent avoidance plays a major role in maintaining anxiety disorders. The few studies that have explored the neural basis of avoidance have predominantly examined established avoidance behaviors rather than the learning processes that establish avoidance responses. We aimed to characterize the temporal dynamics and neural mechanisms of avoidance learning using a novel paradigm combined with 7 tesla fMRI in 82 healthy participants (37 male and 45 female). Participants were first conditioned to two threat stimuli and a compound safety stimulus. Next, they were trained to avoid one threat stimulus while the other remained unavoidable. Behavioral data confirmed accurate learning of task contingencies. Successful avoidance was associated with prominent activation of the ventromedial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), and ventrolateral prefrontal cortex compared with unsuccessful avoidance, with additional nucleus accumbens and orbitofrontal cortex engagement when compared with safety learning (P FDR whole-brain corrected). Critically, early compared with late avoidance learning was distinctly associated with activation of midbrain-striatal circuits, including the periaqueductal gray (PAG), mediodorsal thalamus, substantia nigra, and anterior insular cortex-regions associated with threat processing and learning-related signaling. These findings suggest that initial avoidance learning relies on subcortical threat-responsive and learning-related circuits, whereas established avoidance responses engage cortical safety-processing regions. This dissociation parallels recent findings in safety learning and provides novel mechanistic insights for interventions targeting maladaptive avoidance patterns.
Distinct neocortical regions subserve different sensory functions, yet the cellular features that distinguish neurons across cortical areas remain poorly understood. Layer (L)2/3 pyramidal neurons (PyNs) are generated at similar developmental times throughout the cortex, but whether their morphological and functional properties are shaped by areal identity programs is unclear. Here, we compared L2/3 PyNs in mouse primary somatosensory (S1) and primary visual (V1) cortices (both male and female). We observed pronounced areal differences where V1 neurons exhibited smaller and less complex dendritic arbors and displayed increased intrinsic excitability relative to their counterparts in S1. These differences were present in both juvenile and adult stages, indicating that they emerge early and persist over time. Given prior evidence implicating the transcription factor LHX2 in dendritic arborization, we tested its contribution to these differences. Loss of Lhx2 in E15.5 V1 progenitors did not alter neuronal morphology in V1, in contrast to our previous findings in S1. We found that E15.5 progenitors display lower levels of LHX2 protein in V1 than in S1; therefore, we overexpressed Lhx2 in V1 progenitors and found increased dendritic branching complexity in V1 L2/3 PyNs. Together, these findings identify LHX2 as a molecular regulator that contributes to area-specific structural differentiation of L2/3 PyNs. Our results show that PyNs arising from different regions of the dorsal pallium diverge in morphology and physiology according to the cortical area, suggesting that regionally patterned transcriptional programs help establish functional specialization across the neocortex.
Peripheral taste neurons vary in tuning breadth; some respond selectively to a single stimulus (narrowly tuned), and others respond to multiple stimuli (broadly tuned). How these differences contribute to taste coding remains unclear. We recorded calcium responses from 280 geniculate ganglion neurons to five or seven taste stimuli in male and female mice. Using five stimuli, 47% of neurons were narrowly tuned, while 53% responded to multiple stimuli. Hierarchical cluster analysis revealed five functional groups with five stimuli and six with seven stimuli, suggesting that the number of clusters is sensitive to the stimulus set rather than representing a fixed number of biologically distinct taste neuron "types." Principal component analysis revealed three stimulus categories: (1) bitter, sour, and nonsodium salts (aversive), (2) sucrose and umami (caloric/appetitive), and (3) sodium salts (sodium-specific). Both narrowly tuned and broadly tuned neurons within a single category contributed to this categorization. In contrast, 40% of the neurons were broadly tuned across categories and did not cluster with specific stimulus types. These cross-category neurons were more likely to exhibit mixture subadditivity-lower than additive responses-suggesting they could have a distinct role in encoding intensity or chemical context. Finally, we show Type II taste bud cells are required for representing these categories and mediating mixture subadditivity between sweet and sour stimuli. These results suggest peripheral gustatory neurons primarily function to categorize taste stimuli into three groups. Furthermore, differing roles for narrowly tuned and broadly tuned neurons may be a key organizing principle of peripheral taste representation.
Stress adaptation is critical to maintaining mental and physical health. If acute stress is associated with changes in neuronal activity in many brain regions, how neuronal activity itself is coordinated across regions during stress and how neuronal networks are modified during stress adaptation are unknown. In male rats, we recorded local field potentials (LFPs) from stress-responsive regions, including the prelimbic cortex, anterior cingulate cortex, basolateral amygdala, lateral habenula, and dorsal hippocampus, in rats during repeated stress exposure in a within-subjects design. We characterized network activity by computing cross-region coherence, Granger causality, and phase-amplitude coupling on bipolar derivatives of LFPs. We established a stress adaptation model in rats: the behavioral response to acute 10 min restraint stress returned to baseline after a second restraint 3 h later. The pre-stress state was characterized by robust global network interactions in the theta and gamma bands. The first exposure induced widespread disconnection, whereas following the second one, when rats showed an adaptive response, the connectivity pattern appeared different from that of the pre-stress state. Finally, baseline, stressed, and adaptive states were predicted (>90% accuracy) from network activity. Overall, we showed that the acutely stressed brain state was primarily a state of network disconnection, while stress adaptation was a new network state rather than a return to baseline.
Cerebellar Purkinje cells (PCs) exhibit a unique and highly complex dendritic architecture, which plays a crucial role in integrating synaptic inputs and shaping their physiological properties. However, fine morphological investigation of PCs at the single-cell level is challenging due to the densely packed soma and extensive dendritic arborization. Here, we present stepwise procedures for the sparse labeling of PCs via a viral-mediated approach, enabling detailed two-dimensional dendritic Sholl analysis and three-dimensional spine quantification. We demonstrated high-resolution labeling of PCs through the administration of an adeno-associated virus (AAV) carrying a conditional Cre recombinase-dependent cassette (AAV, CAG-FLEX-EGFP). The AAV was delivered through an intracerebroventricular injection in Pcp2-Cre neonatal mice of either sex. Subsequently, we optimized two analytical pipelines to characterize dendritic complexity and spines. As a sample application, we performed analysis on the labeled PCs from anterior (I-V) and posterior (VI-IX) cerebellar lobules in mice of both sexes. In doing so, we detected an age-dependent, lobule-specific dendritic branching pattern difference. PCs from the anterior lobules exhibited a higher spine density but a smaller spine head diameter compared with those from the posterior lobules. Additionally, we examined PC morphological perturbations in a disease model of Dravet syndrome, a disorder caused by SCN1A haploinsufficiency. Here, we identified reduced dendritic complexity and immature spine morphology in the PCs of Scn1a+/- mice of both sexes. Thus, we provide a labeling method that is easily adaptable, efficient, robust, and well suited for examining PC morphology during cerebellar development and related pathogenic conditions.
Music imagery involves internally generated auditory experiences, yet decoding imagined melodic content from neural activity remains challenging. Here, we examined whether imagined melodies can be decoded from human electrocorticography (ECoG) recordings using a relative pitch framework. Ten epilepsy patients performed a music imagery task involving familiar melodies presented in multiple tonalities (3 males and 7 females; mean age, 27.3 ± 4.69 years). Neural features from imagery-responsive cortical sites were used to train intrasubject models to decode relative pitch classes at the single-note level. Although single-note decoding accuracy was modest, it reliably exceeded chance. Sequential integration of decoded pitch classes enabled reconstruction of melodic contours that preserved the relative structure of imagined melodies. These results provide a proof-of-concept that imagined melodic structure can be accessed from intracranial neural recordings when framed in terms of relative pitch, underscoring the importance of sequence-level approaches for decoding internally generated auditory content.
