The hippocampus and amygdala are functionally coupled brain regions that play a crucial role in processes involving memory and learning. Because interareal communication has been reported both during specific sleep stages and in awake, behaving animals, these brain regions can serve as an archetype to establish that measuring functional interactions is important for comprehending neural systems. To this end, we analyze here a public dataset of local field potentials (LFPs) recorded in rats simultaneously from the hippocampus and amygdala during different behaviors. Employing a specific, time-lagged embedding technique, named topological causality (TC), we infer directed interactions between the LFP band powers of the two regions across six frequency bands in a time-resolved manner. The combined power and interaction signals are processed with our own unsupervised tools developed originally for the analysis of molecular dynamics simulations to effectively visualize and identify putative, neural states that ...

Numerous brain regions have been identified as contributing to withdrawal behaviors, but it is unclear the way in which these brain regions as a whole lead to withdrawal. The search for a final common brain pathway that is involved in withdrawal remains elusive. To address this question, we implanted osmotic minipumps containing either saline, nicotine (24 mg/kg/d), cocaine (60 mg/kg/d), or methamphetamine (4 mg/kg/d) for one week in male C57BL/6J mice. After one week, the minipumps were removed and brains collected 8 h (saline, nicotine, and cocaine) or 12 h (methamphetamine) after removal. We then performed single-cell whole-brain imaging of neural activity during the withdrawal period when brains were collected. We used hierarchical clustering and graph theory to identify similarities and differences in brain functional architecture. Although methamphetamine and cocaine shared some network similarities, the main common neuroadaptation between these psychostimulant drugs was a dramatic decrease in modula...

Time-varying pitch is a vital cue for human speech perception. Neural processing of time-varying pitch has been extensively assayed using scalp-recorded frequency-following responses (FFRs), an electrophysiological signal thought to reflect integrated phase-locked neural ensemble activity from subcortical auditory areas. Emerging evidence increasingly points to a putative contribution of auditory cortical ensembles to the scalp-recorded FFRs. However, the properties of cortical FFRs and precise characterization of laminar sources are still unclear. Here we used direct human intracortical recordings as well as extracranial and intracranial recordings from macaques and guinea pigs to characterize the properties of cortical sources of FFRs to time-varying pitch patterns. We found robust FFRs in the auditory cortex across all species. We leveraged representational similarity analysis as a translational bridge to characterize similarities between the human and animal models. Laminar recordings in animal models ...

Internal affective states produce external manifestations such as facial expressions. In humans, the Facial Action Coding System (FACS) is widely used to objectively quantify the elemental facial action units (AUs) that build complex facial expressions. A similar system has been developed for macaque monkeys—the Macaque FACS (MaqFACS); yet, unlike the human counterpart, which is already partially replaced by automatic algorithms, this system still requires labor-intensive coding. Here, we developed and implemented the first prototype for automatic MaqFACS coding. We applied the approach to the analysis of behavioral and neural data recorded from freely interacting macaque monkeys. The method achieved high performance in the recognition of six dominant AUs, generalizing between conspecific individuals ( Macaca mulatta ) and even between species ( Macaca fascicularis ). The study lays the foundation for fully automated detection of facial expressions in animals, which is crucial for investigating the neural ...

Tracking and quantifying the abundance and location of cells in the developing brain is essential in neuroscience research, enabling a greater understanding of mechanisms underlying nervous system morphogenesis. Widely used experimental methods to quantify cells labeled with fluorescent markers—such as immunohistochemistry, in situ hybridization, and expression of transgenes via stable lines or transient in utero electroporations—depend upon accurate and consistent quantification of images. Current methods to quantify fluorescently-labeled cells rely on labor-intensive manual counting approaches, such as the Fiji plugin Cell Counter , which requires custom macros to enable higher-throughput analyses. Here, we present RapID Cell Counter, a semi-automated cell-counting tool with an easy-to-implement graphical user interface, that facilitates quick and consistent quantifications of cell density within user-defined boundaries that can be divided into equally-partitioned segments. Compared to the standard manua...

With the wide adoption of genomic sequencing in children having seizures, an increasing number of SCN2A genetic variants have been revealed as genetic causes of epilepsy. Voltage-gated sodium channel Nav1.2, encoded by gene SCN2A , is predominantly expressed in the pyramidal excitatory neurons and supports action potential firing. One recurrent SCN2A genetic variant is L1342P, which was identified in multiple patients with epileptic encephalopathy and intractable seizures. However, the mechanism underlying L1342P-mediated seizures and the pharmacogenetics of this variant in human neurons remain unknown. To understand the core phenotypes of the L1342P variant in human neurons, we took advantage of a reference human induced pluripotent stem cell (hiPSC) line from a male donor, in which L1342P was introduced by CRISPR/Cas9 mediated genome editing. Using patch-clamping and micro-electrode array (MEA) recordings, we revealed that cortical neurons derived from hiPSCs carrying heterozygous L1342P variant have sig...

Despite being canonically considered a motor control structure, the cerebellum is increasingly recognized for important roles in processes beyond this traditional framework, including seizure suppression. Excitatory fastigial neurons project to a large number of downstream targets, and it is unclear if this broad targeting underlies seizure suppression, or if a specific output may be sufficient. To address this question, we used the intrahippocampal kainic acid mouse model of temporal lobe epilepsy, male and female animals, and a dual-virus approach to selectively label and manipulate fastigial outputs. We examined fastigial neurons projecting to the superior colliculus, medullary reticular formation, and central lateral nucleus of the thalamus, and found that these comprise largely non-overlapping populations of neurons which send collaterals to unique sets of additional, somewhat overlapping, thalamic and brainstem regions. We found that neither optogenetic stimulation of superior colliculus nor reticula...

Accumulating evidence in the past decade implicates histone modifying enzymes, such as class I histone deacetylases (HDACs), in learning and memory, and recently habit formation. However, it is unclear whether HDACs play roles in complex cognitive function. To address this issue, we examined the role of dorsal striatal HDAC5, a class II HDAC, in reward-guided decision-making and associated neural encoding in rats. We first injected adeno-associated virus to overexpress a nuclear-localized HDAC5 in dorsal striatum (DS). We then recorded neural correlates from dorsolateral striatum (DLS) as rats performed two reward-guided choice tasks, in which we manipulated either the size of or delay to reward. During these tasks, rats first learned which of two options led to the better reward, and then reversed those contingencies in a second block of trials. We found that rats with HDAC5 overexpression in DS responded faster and chose higher value reward more often during the first block of trials, but were less able ...

The primary somatosensory cortex (S1) plays a critical role in processing multiple somatosensations, but the mechanism underlying the representation of different submodalities of somatosensation in S1 remains unclear. Using in vivo two-photon calcium imaging that simultaneously monitors hundreds of layer 2/3 pyramidal S1 neurons of awake male mice, we examined neuronal responses triggered by mechanical, thermal or pruritic stimuli. We found that mechanical, thermal and pruritic stimuli activated largely overlapping neuronal populations in the same somatotopic S1 subregion. Population decoding analysis revealed that the local neuronal population in S1 encoded sufficient information to distinguish different somatosensory submodalities. Although multimodal S1 neurons responding to multiple types of stimuli exhibited no spatial clustering, S1 neurons preferring mechanical and thermal stimuli tended to show local clustering. These findings demonstrated the coding scheme of different submodalities of somatosensa...

Brain-machine interfaces (BMIs) for reaching have enjoyed continued performance improvements, yet there remains significant need for BMIs that control other movement classes. Recent scientific findings suggest that the intrinsic covariance structure of neural activity depends strongly on movement class, potentially necessitating different decode algorithms across classes. To address this possibility, we developed a self-motion BMI based on cortical activity as monkeys cycled a hand-held pedal to progress along a virtual track. Unlike during reaching, we found no high-variance dimensions that directly correlated with to-be-decoded variables. This was due to no neurons having consistent correlations between their responses and kinematic variables. Yet we could decode a single variable – self-motion – by non-linearly leveraging structure that spanned multiple high-variance neural dimensions. Resulting online BMI-control success rates approached those during manual control. These findings make two broad points...