State-dependent Changes Research Articles

Lipid- and protein-directed photosensitizer proximity labeling captures the cholesterol interactome.

The physical properties of cellular membranes, including fluidity and function, are influenced by protein and lipid interactions. In situ labeling chemistries, most notably proximity-labeling interactomics are well suited to characterize these dynamic and often fleeting interactions. Established methods require distinct chemistries for proteins and lipids, which limits the scope of such studies. Here we establish a singlet-oxygen-based photocatalytic proximity labeling platform (POCA) that reports intracellular interactomes for both proteins and lipids with tight spatiotemporal resolution using cell-penetrant photosensitizer reagents. Using both physiologically relevant lipoprotein-complexed probe delivery and genetic manipulation of cellular cholesterol handling machinery, cholesterol-directed POCA captured established and unprecedented cholesterol binding proteins, including protein complexes sensitive to intracellular cholesterol levels and proteins uniquely captured by lipoprotein uptake. Protein-directed POCA accurately mapped known intracellular membrane complexes, defined sterol-dependent changes to the non-vesicular cholesterol transport protein interactome, and captured state-dependent changes in the interactome of the cholesterol transport protein Aster-B. More broadly, we find that POCA is a versatile interactomics platform that is straightforward to implement, using the readily available HaloTag system, and fulfills unmet needs in intracellular singlet oxygen-based proximity labeling proteomics. Thus, we expect widespread utility for POCA across a range of interactome applications, spanning imaging to proteomics.

Re-evaluating the relationship between female social bonds and infant survival in wild baboons.

Over the past few decades studies have provided strong evidence that the robust links between the social environment, health, and survival found in humans also extend to non-human social animals. A number of these studies emphasize the early life origins of these effects. For example, in several social mammals, more socially engaged mothers have infants with higher rates of survival compared to less socially engaged mothers, suggesting that positive maternal social relationships causally improve offspring survival. Here we show that the relationship between infant survival and maternal sociality is confounded by previously underappreciated variation in female social behavior linked to changes in reproductive state and the presence of a live infant. Using data from a population of wild baboons living in the Amboseli basin of Kenya - a population where high levels of maternal sociality have previously been linked to improved infant survival - we find that infant- and reproductive state-dependent changes in female social behavior drive a statistically significant relationship between maternal sociality and infant survival. After accounting for these state-dependent changes in social behavior, maternal sociality is no longer positively associated with infant survival in this population. Our results emphasize the importance of considering multiple explanatory pathways-including third-variable effects-when studying the social determinants of health in natural populations.

Decoding state-dependent cortical-cerebellar cellular functional connectivity in the mouse brain

The cortex and cerebellum form multi-synaptic reciprocal connections. We investigate the functional connectivity between single spiking cerebellar neurons and the population activity of the mouse dorsal cortex using mesoscale imaging. Cortical representations of individual cerebellar neurons vary significantly across different brain states but are drawn from a common set of cortical networks. These cortical-cerebellar connectivity features are observed in mossy fibers and Purkinje cells as well as neurons in different cerebellar lobules, albeit with variations across cell types and regions. Complex spikes of Purkinje cells preferably associate with the sensorimotor cortex, whereas simple spikes display more diverse cortical connectivity patterns. The spontaneous functional connectivity patterns align with cerebellar neurons' functional responses to external stimuli in a modality-specific manner. The tuning properties of subsets of cerebellar neurons differ between anesthesia and awake states, mirrored by state-dependent changes in their long-range functional connectivity patterns with mesoscale cortical activity.

Unveiling Valence State-Dependent Photocatalytic Water Splitting Activity and Photocathodic Behavior in Visible Light-Active Iridium-Doped BaTiO3.

Despite having favorable energetics and tunable optoelectronic properties, utilization of BaTiO3 (BTO) for photocatalytic reactions is limited by its absorption only in the ultraviolet region. To address this challenge, BTO is doped with iridium (Ir) to induce visible light absorption. The visible light-induced photocatalytic H2 generation efficiency is enhanced by 2 orders of magnitude on selective conversion of the Ir valence state from Ir4+ to Ir3+. To understand such intriguing behavior, valence state-dependent changes in the optoelectronic, structural, and surface properties and electronic band structure are comprehensively investigated. The effect of electron occupancy change between Ir4+ (t2g5 eg0) and Ir3+ (t2g6 eg0) and their energetic positions within the band gap is found to significantly influence H2 generation. Besides this, converting Ir4+ to Ir3+ enhanced the photocathodic current and lowered the onset potential. Results aid in designing photocatalysts to efficiently use low-energy photons for enhancing solar H2 production in these emerging BTO-based photocatalysts. Collectively, the observations made in this work highlight the promising application of Ir3+:BTO in z-scheme photocatalysis.

Traumatic brain injury disrupts state-dependent functional cortical connectivity in a mouse model.

Traumatic brain injury (TBI) is the leading cause of death in young people and can cause cognitive and motor dysfunction and disruptions in functional connectivity between brain regions. In human TBI patients and rodent models of TBI, functional connectivity is decreased after injury. Recovery of connectivity after TBI is associated with improved cognition and memory, suggesting an important link between connectivity and functional outcome. We examined widespread alterations in functional connectivity following TBI using simultaneous widefield mesoscale GCaMP7c calcium imaging and electrocorticography (ECoG) in mice injured using the controlled cortical impact (CCI) model of TBI. Combining CCI with widefield cortical imaging provides us with unprecedented access to characterize network connectivity changes throughout the entire injured cortex over time. Our data demonstrate that CCI profoundly disrupts functional connectivity immediately after injury, followed by partial recovery over 3weeks. Examining discrete periods of locomotion and stillness reveals that CCI alters functional connectivity and reduces theta power only during periods of behavioral stillness. Together, these findings demonstrate that TBI causes dynamic, behavioral state-dependent changes in functional connectivity and ECoG activity across the cortex.

Motion state-dependent motor learning based on explicit visual feedback has limited spatiotemporal properties compared with adaptation to physical perturbations.

We recently showed that subjects can learn motion state-dependent changes to motor output (temporal force patterns) based on explicit visual feedback of the equivalent force field (i.e., without the physical perturbation). Here, we examined the spatiotemporal properties of this learning compared with learning based on physical perturbations. There were two human subject groups and two experimental paradigms. One group (n = 40) experienced physical perturbations (i.e., a velocity-dependent force field, vFF), whereas the second (n = 40) was given explicit visual feedback (EVF) of the force-velocity relationship. In the latter, subjects moved in force channels and we provided visual feedback of the lateral force exerted during the movement, as well as the required force pattern based on movement velocity. In the first paradigm (spatial generalization), following vFF or EVF training, generalization of learning was tested by requiring subjects to move to 14 untrained target locations (0° to ±135° around the trained location). In the second paradigm (temporal stability), following training, we examined the decay of learning over eight delay periods (0 to 90 s). Results showed that learning based on EVF did not generalize to untrained directions, whereas the generalization for the vFF was significant for targets ≤ 45° away. In addition, the decay of learning for the EVF group was significantly faster than the FF group (a time constant of 2.72 ± 1.74 s vs. 12.53 ± 11.83 s). Collectively, our results suggest that recalibrating motor output based on explicit motion state information, in contrast to physical disturbances, uses learning mechanisms with limited spatiotemporal properties.NEW & NOTEWORTHY Adjustment of motor output based on limb motion state information can be achieved based on explicit information or from physical perturbations. Here, we investigated the spatiotemporal characteristics of short-term motor learning to determine the properties of the respective learning mechanisms. Our results suggest that adjustments based on physical perturbations are more temporally stable and applied over a greater spatial range than the learning based on explicit visual feedback, suggesting largely separate learning mechanisms.

Imaging microglia surveillance during sleep-wake cycles in freely behaving mice

Microglia surveillance manifests itself as dynamic changes in cell morphology and functional remodeling. Whether and how microglia surveillance is coupled to brain state switches during natural sleep-wake cycles remains unclear. To address this question, we used miniature two-photon microscopy (mTPM) to acquire time-lapse high-resolution microglia images of the somatosensory cortex, along with EEG/EMG recordings and behavioral video, in freely-behaving mice. We uncovered fast and robust brain state-dependent changes in microglia surveillance, occurring in parallel with sleep dynamics and early-onset phagocytic microglial contraction during sleep deprivation stress. We also detected local norepinephrine fluctuation occurring in a sleep state-dependent manner. We showed that the locus coeruleus-norepinephrine system, which is crucial to sleep homeostasis, is required for both sleep state-dependent and stress-induced microglial responses and β2-adrenergic receptor signaling plays a significant role in this process. These results provide direct evidence that microglial surveillance is exquisitely tuned to signals and stressors that regulate sleep dynamics and homeostasis so as to adjust its varied roles to complement those of neurons in the brain. In vivo imaging with mTPM in freely behaving animals, as demonstrated here, opens a new avenue for future investigation of microglia dynamics and sleep biology in freely behaving animals.

Imaging microglia surveillance during sleep-wake cycles in freely behaving mice.

Microglia surveillance manifests itself as dynamic changes in cell morphology and functional remodeling. Whether and how microglia surveillance is coupled to brain state switches during natural sleep-wake cycles remains unclear. To address this question, we used miniature two-photon microscopy (mTPM) to acquire time-lapse high-resolution microglia images of the somatosensory cortex, along with EEG/EMG recordings and behavioral video, in freely-behaving mice. We uncovered fast and robust brain state-dependent changes in microglia surveillance, occurring in parallel with sleep dynamics and early-onset phagocytic microglial contraction during sleep deprivation stress. We also detected local norepinephrine fluctuation occurring in a sleep state-dependent manner. We showed that the locus coeruleus-norepinephrine system, which is crucial to sleep homeostasis, is required for both sleep state-dependent and stress-induced microglial responses and β2-adrenergic receptor signaling plays a significant role in this process. These results provide direct evidence that microglial surveillance is exquisitely tuned to signals and stressors that regulate sleep dynamics and homeostasis so as to adjust its varied roles to complement those of neurons in the brain. In vivo imaging with mTPM in freely behaving animals, as demonstrated here, opens a new avenue for future investigation of microglia dynamics and sleep biology in freely behaving animals.

Functional plasticity of the swim bladder as an acoustic organ for communication in a vocal fish.

Teleost fishes have evolved a number of sound-producing mechanisms, including vibrations of the swim bladder. In addition to sound production, the swim bladder also aids in sound reception. While the production and reception of sound by the swim bladder has been described separately in fishes, the extent to which it operates for both in a single species is unknown. Here, using morphological, electrophysiological and modelling approaches, we show that the swim bladder of male plainfin midshipman fish (Porichthys notatus) exhibits reproductive state-dependent changes in morphology and function for sound production and reception. Non-reproductive males possess rostral 'horn-like' swim bladder extensions that enhance low-frequency (less than 800 Hz) sound pressure sensitivity by decreasing the distance between the swim bladder and inner ear, thus enabling pressure-induced swim bladder vibrations to be transduced to the inner ear. By contrast, reproductive males display enlarged swim bladder sonic muscles that enable the production of advertisement calls but also alter swim bladder morphology and increase the swim bladder to inner ear distance, effectively reducing sound pressure sensitivity. Taken together, we show that the swim bladder exhibits a seasonal functional plasticity that allows it to effectively mediate both the production and reception of sound in a vocal teleost fish.

Measuring the reliability of binocular rivalry.

Binocular rivalry is a widely used tool in sensory and cognitive neuroscience to investigate different aspects of vision and cognition. The dynamics of binocular rivalry (e.g., duration of perceptual dominance phases and mixed percept proportions) differ across individuals; based on rivalry dynamics, it is also possible to calculate an index of ocular dominance (by comparing the perceptual dominance of the images in the two eyes). In this study, we investigated the reliability of binocular rivalry dynamics using different methods for dichoptic stimulation and different rivalry stimuli. For the three main indices we defined (ocular dominance, phase durations and mixed percept proportions), we found a high test-retest reliability across sessions. Moreover, the test-retest reliability of the ocular dominance index was predictable from its internal consistency, supporting its stability over time. Phase durations and mixed percept proportions, in contrast, had worse test-retest reliability than expected based on internal consistency, indicating that these parameters are susceptible to state-dependent changes. Our results support the use of the ocular dominance index and binocular rivalry in the measurement of sensory eye dominance and its plasticity, but advise caution when investigating the association between phase durations or mixed percepts and stable characteristics like psychological traits or disorders.

Social problem-solving and suicidal behavior in adolescent girls: A prospective examination of proximal and distal social stress-related risk factors.

Adverse social experiences are often linked to suicidal behavior in adolescence, perhaps particularly for girls. Social problem-solving abilities may indicate more or less adaptive responses to adverse social experiences that contribute to adolescent girls' risk for suicidal behavior. While social problem-solving is implicated in cognitive and behavioral theories of suicidal behavior, prior work is largely cross-sectional and examines bivariate associations between social problem-solving, assessed in neutral conditions, and suicidal behavior. Using a novel performance-based task, this study assessed social problem-solving in adolescent girls (N = 185, Mage = 14.66, SD = 1.41) before and after an experimentally simulated social stressor and examined associations between social problem-solving and past-year suicidal behavior. Prospective analyses tested whether greater changes in specific social problem-solving domains following the social stressor predicted greater likelihood of suicidal behavior over a 9-month follow-up in contexts of elevated, real-life interpersonal stress. Results revealed that adolescent girls who showed greater changes (i.e., reflecting declines) in problem-solving effectiveness following acute social stress were more likely to exhibit suicidal behavior over the following 9 months, but only if they also experienced elevated interpersonal stress in real life. State-dependent changes in social problem-solving may indicate a cognitive vulnerability following social stress that, in combination with cumulative interpersonal stress in real life, distinguishes adolescent girls at heightened risk for future suicidal behavior. Findings demonstrate the importance of examining suicide risk factors under conditions that may more closely mirror the interpersonal contexts in which adolescents' risk for suicidal behavior may be elevated. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Molecular rearrangements in S6 during slow inactivation in Shaker-IR potassium channels.

Voltage-gated K+ channels have distinct gates that regulate ion flux: the activation gate (A-gate) formed by the bundle crossing of the S6 transmembrane helices and the slow inactivation gate in the selectivity filter. These two gates are bidirectionally coupled. If coupling involves the rearrangement of the S6 transmembrane segment, then we predict state-dependent changes in the accessibility of S6 residues from the water-filled cavity of the channel with gating. To test this, we engineered cysteines, one at a time, at S6 positions A471, L472, and P473 in a T449A Shaker-IR background and determined the accessibility of these cysteines to cysteine-modifying reagents MTSET and MTSEA applied to the cytosolic surface of inside-out patches. We found that neither reagent modified either of the cysteines in the closed or the open state of the channels. On the contrary, A471C and P473C, but not L472C, were modified by MTSEA, but not by MTSET, if applied to inactivated channels with open A-gate (OI state). Our results, combined with earlier studies reporting reduced accessibility of residues I470C and V474C in the inactivated state, strongly suggest that the coupling between the A-gate and the slow inactivation gate is mediated by rearrangements in the S6 segment. The S6 rearrangements are consistent with a rigid rod-like rotation of S6 around its longitudinal axis upon inactivation. S6 rotation and changes in its environment are concomitant events in slow inactivation of Shaker KV channels.

A mammal and bird's-eye-view of the pupil during sleep and wakefulness.

Besides regulating the amount of light that reaches the retina, fluctuations in pupil size also occur in isoluminant conditions during accommodation, during movement and in relation to cognitive workload, attention and emotion. Recent studies in mammals and birds revealed that the pupils are also highly dynamic in the dark during sleep. However, despite exhibiting similar sleep states (rapid eye movement [REM] and non-REM [NREM] sleep), wake and sleep state-dependent changes in pupil size are opposite between mammals and birds, due in part to differences in the type (striated vs. smooth) and control of the iris muscles. Given the link between pupil dynamics and cognitive processes occurring during wakefulness, sleep-related changes in pupil size might indicate when related processes are occurring during sleep. Moreover, the divergent pupillary behaviour observed between mammals and birds raises the possibility that changes in pupil size in birds are a readout of processes not reflected in the mammalian pupil.

Initial development and validation of a brief assessment of marijuana demand among young adult college students.

Hypothetical purchase tasks assess substance demand, but the length of purchase tasks makes repeated assessment of state-dependent changes in demand difficult, often limiting clinical utility. Although brief assessments of alcohol and cigarette demand exist, brief measures of cannabis demand do not. College students (N = 209, Mage = 19.92, SD = 1.45; 63% female; 56.9% non-Hispanic Caucasian) who reported using cannabis at least 3 days in the past month, completed an online survey including the full-length marijuana purchase task (MPT), a three-item brief assessment of marijuana demand (BAMD) assessing intensity, Omax and breakpoint, and cannabis use outcomes. Convergent and divergent validity were examined. Independent samples t tests compared demand on the BAMD and MPT based on presence or absence of cannabis use disorder (CUD) symptoms, and one-way between-subject analyses of variance compared effects of CUD severity (mild/moderate/severe) on BAMD indices. All indices were significantly correlated across both assessment measures (ps < .01). Similarly, all indices on both demand measures were significantly correlated with craving, CUD severity, and cannabis-related consequences (ps < .01); whereas only intensity and Omax were significantly correlated with cannabis use frequency (ps < .01). Individuals with (vs. without) CUD symptoms reported significantly greater intensity and Omax (ps < .01) and significant differences in CUD severity on BAMD indices were found as well (ps < .05). The BAMD demonstrated convergent and divergent validity with the MPT. Findings suggest that brief cannabis demand can be easily assessed as an indicator for high-risk cannabis use. Thus, the BAMD may be a useful and clinically relevant tool to assess cannabis demand in real-world settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

State-dependent interhemispheric inhibition reveals individual differences in motor behavior in chronic stroke

ObjectiveTo investigate state-dependent interhemispheric inhibition (IHI) in chronic stroke survivors compared to neurotypical older adult controls, and test whether abnormal IHI modulation was associated with upper extremity motor behavior. MethodsDual-coil transcranial magnetic stimulation (TMS) measured IHI bi-directionally, between non-lesioned and lesioned motor cortex (M1) in two activity states: (1) at rest and (2) during contralateral isometric hand muscle contraction. IHI was tested by delivering a conditioning stimulus 8-msec or 50-msec prior to a test stimulus over contralateral M1. Paretic motor behavior was assessed by clinical measures of impairment, strength, and dexterity, and mirroring activity in the non-paretic hand. ResultsStroke survivors demonstrated reduced IHI at rest, and less IHI modulation (active – rest) compared to controls. Individual differences in IHI modulation were related to motor behavior differences where greater IHI modulation was associated with greater motor impairment and more mirroring. In contrast, there were no relationships between IHI at rest and motor behavior. ConclusionsAbnormal state-dependent interhemispheric circuit activity may be more sensitive to post-stroke motor deficits than when assessed in a single motor state. SignificanceCharacterizing state-dependent changes in neural circuitry may enhance models of stroke recovery and inform rehabilitation interventions.

Effects of neuromodulation-inspired mechanisms on the performance of deep neural networks in a spatial learning task

In recent years, the biological underpinnings of adaptive learning have been modeled, leading to faster model convergence and various behavioral benefits in tasks including spatial navigation and cue-reward association. Furthermore, studies have investigated how the neuromodulatory system, a major driver of synaptic plasticity and state-dependent changes in the brain neuronal activities, plays a role in training deep neural networks (DNNs). In this study, we extended previous studies on neuromodulation-inspired DNNs and explored the effects of neuromodulatory components on learning and single unit activities in a spatial learning task. Under the multiscale neuromodulatory framework, plastic components, dropout probability modulation, and learning rate decay were added to the single unit, layer, and whole network levels of DNN models, respectively. We observed behavioral benefits including faster learning and smaller error of ambulation. We then concluded that neuromodulatory components can affect learning trajectories, outcomes, and single unit activities, in a component- and hyperparameter-dependent manner.

Trait- and State-Dependent Changes in Cortical-Subcortical Functional Networks Across the Adult Lifespan.

How the functional interactions of the basal ganglia/thalamus with the cerebral cortex and the cerebellum change over the adult lifespan in movie-watching and resting-state is less clear. To investigate the functional changes in the organization of the human cortical-subcortical functional networks over the adult lifespan using movie-watching and resting-state fMRI data. Cohort. Healthy 467 adults (cross-sectional individuals aged 18-88 years) from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.com). FIELD STRENGTH/SEQUENCE: fMRI using a gradient-echo echo-planar imaging (EPI) sequence at 3T. Functional connectivities (FCs) of the subcortical subregions (i.e. the basal ganglia and thalamus) with both the cerebral cortex and cerebellum were examined in fMRI data acquired during resting state and movie-watching. And, fluid intelligence scores were also assessed. Student's t-tests, false discovery rate (FDR) corrected. As age increased, FCs that mainly within the basal ganglia and thalamus, and between the basal ganglia/thalamus and cortical networks (including the dorsal attention, ventral attention, and limbic networks) were both increased/decreased during movie-watching and resting states. However, FCs showed a state-dependent component with advancing age. During the movie-watching state, the FCs between the basal ganglia/thalamus and cerebellum/frontoparietal control networks were mainly increased with age, and the FCs in the somatomotor network were decreased with age. During the resting state, the FCs between the basal ganglia/thalamus and default mode/visual networks were mainly increased with age, and the FCs in the cerebellum were mainly decreased with age. Moreover, inverse relationships between FCs and fluid intelligence were mainly found in these network regions. Our study may suggest that changes in cortical-subcortical functional networks across the adult lifespan were both state-dependent and stable traits, and that aging fMRI studies should consider the effects of both physiological characteristics and individual situations. 2. Stage 3.

Behavioral status modulates CA2 influence on hippocampal network dynamics.

Dynamic interactions between the subregions of the hippocampus are required for the encoding and consolidation of memory. While the interplay and contributions of the CA1 and CA3 regions are well understood, we continue to learn more about how CA2 differentially contributes to the organization of network function. For example, CA2 place cells have been reported to be less spatially tuned during exploration, but uniquely capable of coding place while an animal stops. Here we applied chemogenetics to transiently silence CA2 pyramidal cells and found that CA2 influences hippocampal dynamics in a state-dependent manner. We find that during rest, CA2 inhibition reduces synchronization across regions (CA1, CA2, CA3) and frequency bands (low-gamma- and ripple-band). Moreover, during new learning CA1 place field formation is slower in the absence of CA2 transmission and during pausing, CA1 pyramidal cells are less excitable without CA2 drive. On the network level, a novel convolutional neural network (SpikeDecoder) was employed to show subregion and state-dependent changes in spatial coding that agree with our observations on the single cell level. Together these data suggest additional novel roles for CA2 in governing and differentiating hippocampal dynamics under discrete behavioral states.

Ion-channel degeneracy and heterogeneities in the emergence of complex spike bursts in CA3 pyramidal neurons.

Complex spike bursting (CSB) is a characteristic electrophysiological signature exhibited by several neuronal subtypes and has been implicated in neural plasticity, learning, perception, anaesthesia and active sensing. Here, we address how pronounced intrinsic and synaptic heterogeneities affect CSB, with hippocampal CA3 pyramidal neurons (CA3PNs), where CSB emergence and heterogeneities are well characterized, as a substrate. We randomly generated 12,000 unique models and found 236 valid models that satisfied 11 characteristic CA3PN measurements. These morphologically and biophysically realistic valid models accounted for gating kinetics and somatodendritic expression profiles of 10 active ion channels. This heterogeneous population of valid models was endowed with broad distributions of underlying parameters showing weak pairwise correlations. We found two functional subclasses of valid models, intrinsically bursting and regular spiking, with significant differences in the expression of calcium and calcium-activated potassium conductances. We triggered CSB in all 236models through different intrinsic or synaptic protocols and observed considerable heterogeneity in CSB propensity and properties spanning models and protocols. Finally, we used virtual knockout analyses and showed that synergistic interactions between intrinsic and synaptic mechanisms regulated CSB emergence and dynamics. Specifically, although there was a dominance of calcium and calcium-activated potassium channels in the emergence of CSB, individual deletion of none of the several ion channels or N-methyl-d-aspartate receptors resulted in the complete elimination of CSB across all models. Together, our analyses critically implicate ion-channel degeneracy in the robust emergence of CSB and other characteristic signatures of CA3PNs, despite pronounced heterogeneities in underlying intrinsic and synaptic properties. KEY POINTS: An unbiased stochastic search algorithm yielded a heterogeneous population of morphologically and biophysically realistic CA3 pyramidal neuronal models matching several signature electrophysiological characteristics. Two functional subclasses of valid models were identified with intrinsically bursting (IB) and regular spiking (RS) characteristics, which exhibited differential localization within the parametric space with linear and non-linear dimension reduction analyses. Calcium and calcium-activated potassium channels distinguished IB from RS models, apart from playing dominant roles in the emergence of complex spike bursting (CSB). The impact of deleting individual ion channels or N-methyl-d-aspartate receptors was variable across different models and differential for each channel/receptor, pointing to ion-channel degeneracy in the emergence of CSB. Biological heterogeneities across different neurons of the same subtype, ion-channel degeneracy and state-dependent changes (involving activity-dependent plasticity, pathology, and neuromodulation of intrinsic and synaptic properties) need to be considered carefully in assessing the propensity and dynamicsof CSB in different neuronal subtypes.

Cortical sensory processing across motivational states during goal-directed behavior

Behavioral states can influence performance of goal-directed sensorimotor tasks. Yet, it is unclear how altered neuronal sensory representations in these states relate to task performance and learning. We trained water-restricted mice in a two-whisker discrimination task to study cortical circuits underlying perceptual decision-making under different levels of thirst. We identified somatosensory cortices as well as the premotor cortex as part of the circuit necessary for task execution. Two-photon calcium imaging in these areas identified populations selective to sensory or motor events. Analysis of task performance during individual sessions revealed distinct behavioral states induced by decreasing levels of thirst-related motivation. Learning was better explained by improvements in motivational state control rather than sensorimotor association. Whisker sensory representations in the cortex were altered across behavioral states. In particular, whisker stimuli could be better decoded from neuronal activity during high task performance states, suggesting that state-dependent changes of sensory processing influence decision-making.