The human medial parietal cortex (MPC) is recruited during multiple cognitive processes. Previously, we demonstrated regions specific to recall of people or places and proposed that the functional organization of MPC mirrors the category selectivity defining the medial–lateral axis of the ventral–temporal cortex (VTC). However, prior work considered recall of people and places only, and VTC also shows object selectivity sandwiched between face- and scene-selective regions. Here, we tested a strong prediction of our proposal: like VTC, MPC should show a region specifically recruited during object recall, and its relative cortical position should mirror the one of VTC. While responses during people and place recall showed a striking replication of prior findings, we did not observe any evidence for object-recall effects within MPC, which differentiates it from the spatial organization in VTC. Importantly, beyond MPC, robust recall effects were observed for people, places, and objects on the lateral surface o...

Epilepsy–aphasia syndrome (EAS) is a spectrum of childhood disorders that exhibit complex comorbidities that include epilepsy and the emergence of cognitive and language disorders. CNKSR2 is an X-linked gene in which mutations are linked to EAS. We previously demonstrated Cnksr2 knock-out (KO) mice model key phenotypes of EAS analogous to those present in clinical patients with mutations in the gene. Cnksr2 KO mice have increased seizures, impaired learning and memory, increased levels of anxiety, and loss of ultrasonic vocalizations (USVs). The intricate interplay between these diverse phenotypes at the brain regional and cell-type level remains unknown. Here, we leverage conditional deletion of the X-linked Cnksr2 in a neuronal cell-type manner in male mice to demonstrate that anxiety and impaired USVs track with its loss from excitatory neurons. Finally, we further narrow the essential role of Cnksr2 loss in USV deficits to excitatory neurons of the ACC, a region in mice recently implicated in USV produ...

Hydroxychloroquine (HCQ), a well-known antimalarial and anti-inflammatory drug, has demonstrated potential neuroprotective effects in ischemic stroke by inhibiting pyroptosis, a programmed cell death associated with inflammation. This study investigates the impact of HCQ on ischemic stroke pathology using both in vivo and in vitro models. In vivo, C57BL/6 mice subjected to middle cerebral artery occlusion (MCAO) were treated with HCQ. Neurological deficits, infarct volume, and the expression of pyroptosis markers were evaluated. The results demonstrated that HCQ significantly improved motor function and reduced infarct volume in the MCAO mouse model. In vitro, BV2 microglial cells exposed to lipopolysaccharide (LPS) and oxygen–glucose deprivation (OGD) were treated with HCQ. Western blot and immunofluorescence analyses revealed that HCQ effectively suppressed the expression of pyroptosis markers GSDMD and NLRP3 in both in vivo and in vitro models. These findings suggest that HCQ mitigates ischemic stroke d...

Epilepsy, a neurological disorder characterized by recurrent unprovoked seizures, significantly impacts patient quality of life. Current classification methods focus primarily on clinical observations and electroencephalography (EEG) analysis, often overlooking the underlying dynamics driving seizures. This study uses surface EEG data to identify seizure transitions using a dynamical systems–based framework—the taxonomy of seizure dynamotypes—previously examined only in invasive data. We applied principal component and independent component (IC) analysis to surface EEG recordings from 1,177 seizures in 158 patients with focal epilepsy, decomposing the signals into ICs. The ICs were visually labeled for clear seizure transitions and bifurcation morphologies (BifMs), which were then examined using Bayesian multilevel modeling in the context of clinical factors. Our analysis reveals that certain onset bifurcations (saddle node on invariant circle and supercritical Hopf) are more prevalent during wakefulness c...

A comprehensive analysis of everyday sound perception can be achieved using electroencephalography (EEG) with the concurrent acquisition of information about the environment. While extensive research has been dedicated to speech perception, the complexities of auditory perception within everyday environments, specifically the types of information and the key features to extract, remain less explored. Our study aims to systematically investigate the relevance of different feature categories: discrete sound-identity markers, general cognitive state information, and acoustic representations, including discrete sound onset, the envelope, and mel-spectrogram. Using continuous data analysis, we contrast different features in terms of their predictive power for unseen data and thus their distinct contributions to explaining neural data. For this, we analyze data from a complex audio-visual motor task using a naturalistic soundscape. The results demonstrated that the feature sets that explain the most neural varia...

It is widely believed that axons in the central nervous system of adult mammals do not regrow following injury. This failure is thought, at least in part, to underlie the limited recovery of function following injury to the brain or spinal cord. Some studies of fixed tissue have suggested that, counter to dogma, norepinephrine (NE) axons regrow following brain injury. Here, we have used in vivo two-photon microscopy in layer 1 of the primary somatosensory cortex in transgenic mice harboring a fluorophore selectively expressed in NE neurons. This protocol allowed us to explore the dynamic nature of NE axons following injury with the selective NE axon toxin N -(2-chloroethyl)- N -ethyl-2-bromobenzylamine (DSP4). Following DSP4, NE axons were massively depleted and then slowly and partially recovered their density over a period of weeks. This regrowth was dominated by new axons entering the imaged volume. There was almost no contribution from local sprouting from spared NE axons. Regrown axons did not appear ...

Cuprizone (CPZ) is a widely used toxin that induces demyelinating diseases in animal models, producing multiple sclerosis (MS)-like pathology in rodents. CPZ is one of the few toxins that triggers demyelination and subsequent remyelination following the cessation of its application. This study examines the functional consequences of CPZ-induced demyelination and the subsequent recovery of neural communication within the anterior cingulate cortex (ACC), with a particular focus on interhemispheric connectivity via the corpus callosum (CC). By employing wide-field, high-speed, voltage-sensitive dye imaging, we were able to provide real-time mapping of neural activity in the ACC of CPZ-fed mice. Although we could not record physiological signals from the CC, the results demonstrated a notable impairment in interhemispheric connections within the ACC via the CC, with the most pronounced loss observed in a specific coronal slice among a series of slices examined. Notably, the latency of neural signal propagation...

The full complement of ion channels which influence insect auditory mechanotransduction and the mechanisms by which their influence is exerted remain unclear. Shal (Kv4), a Shaker family member encoding voltage-gated potassium channels in Drosophila melanogaster , has been shown to localize to dendrites in some neuron types, suggesting the potential role of Shal in Drosophila hearing, including mechanotransduction. A GFP trap was used to visualize the localization of the Shal channel in Johnston's organ neurons responsible for hearing in the antenna. Shal protein was localized strongly to the cell body and inner dendritic segment of sensory neurons. It was also detectable in the sensory cilium, suggesting its involvement not only in general auditory function but specifically in mechanotransduction. Electrophysiological recordings to assess neural responses to auditory stimuli in mutant Shal flies revealed significant decreases in auditory responses. Laser Doppler vibrometer recordings indicated abnormal an...

A unique pool of immature glutamatergic neurons in the primate amygdala, known as the paralaminar nucleus (PL), are maturing between infancy and adolescence. The PL is a potential substrate for the steep growth curve of amygdala volume during this developmental period. A microglial component is also embedded among the PL neurons and likely supports local neuronal maturation and emerging synaptogenesis. Microglia may alter neuronal growth following environmental perturbations such as stress. Using multiple measures in rhesus macaques, we found that microglia in the infant primate PL had relatively large somas and a small arbor size. In contrast, microglia in the adolescent PL had a smaller soma and a larger dendritic arbor. We then examined microglial morphology in the PL after a novel maternal separation protocol, to examine the effects of early life stress. After maternal separation, the microglia had increased soma size, arbor size, and complexity. Surprisingly, strong effects were seen not only in the i...

The social environment has long been recognized to play an important role in substance use, which is often modeled in rodents using operant conditioning. However, most operant chambers only accommodate one rodent at a time. We present PeerPub—a unique social operant chamber. PeerPub employs touch sensors to track the licking behavior on drinking spouts. When the number of licks meets a set reinforcement schedule, it dispenses a drop of solution with a fixed volume as a reward at the tip of the spout. A radio frequency identification (RFID) chip implanted in each rat’s skull identifies it throughout the experiment. The system is managed by a Raspberry Pi computer. We evaluated PeerPub using Sprague Dawley rats in daily 1 h sessions, where supersac (a glucose and saccharin solution) was provided under a fixed-ratio five schedule. We discovered that male rats consumed more supersac in dual rat conditions compared with single rat conditions. These findings illustrate PeerPub’s effectiveness in modeling the int...