Neurons couple to various degrees to the activity level of the local neighboring population whereby strongly coupled “choristers” and weakly coupled “soloists” have been identified as two extremes of a continuous spectrum. At the same time neuronal populations undergo coordinated ON and OFF cortical state activity fluctuations, which are locally modulated by attention. The population coupling of soloists and choristers suggests that soloists should show limited alignment with cortical state fluctuations, while choristers should exhibit profound alignment. To test this, we recorded neurons across cortical layers in macaque areas V1 and V4 ( n  = 2 males), while animals performed a feature-based spatial attention task. As expected, we found a wide range of population coupling strength of neurons. In line with our prediction, coupling of choristers to cortical state changes (ON-OFF transitions) was generally stronger than that of soloists. The strength of population coupling of neurons was similar during spon...

Ischemic stroke, a leading cause of neurological morbidity, is characterized by extensive neuronal injury and a robust inflammatory response. Erbin, a scaffold protein involved in multiple cellular signaling pathways, regulates neuroinflammation and may confer neuroprotection against ischemia–reperfusion (I/R) injury. A mouse model of middle cerebral artery occlusion was utilized to evaluate the neuroprotective role of Erbin. Male mice were allocated into groups receiving either a lentiviral (LV) control vector or LV-mediated Erbin overexpression, followed by I/R injury induction. Neurological function, infarct volume, and expression levels of inflammatory cytokines and mitogen-activated protein kinase (MAPK) signaling proteins were analyzed. Overexpression of Erbin via LV transduction significantly reduced cerebral infarct volume and mitigated neurological impairments post-I/R injury. Furthermore, Erbin overexpression suppressed the phosphorylation of p38 and extracellular signal-regulated kinase in HT22 ...

Following a traumatic brain injury (TBI), the neocortex undergoes time-dependent cellular responses including immediate tissue deformation, enhanced excitability, and elevated expression of immediate early genes. However, the spatial extent of early neuronal activity after a focal injury remains unclear. Here we use targeted recombination in active populations reporter mice of both sexes to identify neurons activated in the acute phase following a controlled cortical impact injury applied to the somatosensory neocortex. We find widespread cell activation across large portions of the cortex that extends beyond the astrocytic and microglial responses marking the injury site. Activated cells are predominantly neurons, and few cells colabel with GFAP or IBA1. Our findings reveal that even focal injury engages cortical circuits across large portions of the injured brain, highlighting the importance of considering cortex-wide neuronal dynamics in the early postinjury period and their potential impact on network ...

Spiking thresholds in neurons or rectification at synapses are essential for neuronal computations rendering neuronal processing inherently nonlinear. Nevertheless, linear response theory has been instrumental for understanding, for example, the impact of noise or neuronal synchrony on signal transmission, or the emergence of oscillatory activity, but is valid only at low stimulus amplitudes or large levels of intrinsic noise. At higher signal-to-noise ratios, however, nonlinear response components become relevant. Theoretical results for leaky integrate-and-fire neurons in the weakly nonlinear regime suggest strong responses at the sum of two input frequencies if one of these frequencies or their sum matches the neuron’s baseline firing rate. We here analyze nonlinear responses in two types of primary electroreceptor afferents, the P-units of the active and the ampullary cells of the passive electrosensory system of the wave-type electric fish Apteronotus leptorhynchus of either sex. In our combined exper...

The retina encodes a broad range of stimuli, adapting its computations to features like brightness, contrast, and motion. However, it is unclear whether it also adapts when switching between natural scenes and white noise (WN). To address this, we analyzed the neural activity of male marmoset retinal ganglion cells (RGCs) in response to WN and naturalistic movies. We trained linear–nonlinear models on both stimuli, evaluated their performance, and compared their receptive fields across stimulus domains. We found that models with spatial filters trained on one stimulus ensemble were less accurate when predicting neural activity on the other compared to models trained directly on the target stimulus. This suggests that spatial processing adapts to stimulus statistics. Different RGC types exhibited distinct changes: The OFF midget cells’ receptive fields became enlarged under natural movies (NMs), resulting in a lower cutoff frequency. Parasol cells and large OFF cells did not significantly change their recep...

Complex problems often allow multiple paths to a solution. Choosing and taking the best path is an important part of the executive cognition that underpins intelligent problem-solving behavior. However, once a path is chosen, the motor system must be activated for executing it. This interface between problem-solving and self-generated action has rarely been studied. We recorded EEG movement-related potentials while 25 participants (7 males, 18 females) performed the “Tower of London” problem-solving task. In a control condition, participants merely followed instructed steps without planning for any goal and thus without any sense that their movements solved a problem. Readiness potentials (RPs) preceding actions showed a more sustained preparatory negativity for self-generated than stimulus-driven movements. Critically, this effect was most pronounced at the first move of a sequence and diminished at later stages, indicating that preparatory activity is closely linked to the planning demands of sequence in...

This study used machine learning to objectively identify seizures in the electroencephalogram of a model of post-traumatic epilepsy based on fluid percussion injury in male rats. We applied transfer learning to a neural-network trained and tested on three potentially distinct electroencephalographic phenotypes: (1) late-onset convulsive seizures associated with rare post-traumatic epilepsy, (2) early-onset convulsive seizures that often occurred after sham or injury treatment (independent of post-traumatic epilepsy), and (3) spike-wave discharges (SWDs), which occurred in both injured and sham-control rats. The neural network was able to detect seizure events within individual animals and across different cohorts and showed that early and late seizures have similar electroencephalographic phenotypes. Additionally, cross-over training and testing on SWDs from injured and sham-control rats distinguished a convulsive seizure phenotype from normal SWDs. Convolutional neural network modeling of the electroencep...

Olfactory anhedonia and heightened aversion to unpleasant odors are well-documented features of depression in humans, yet the neural mechanisms linking chronic stress to altered olfactory perception remain poorly understood. We used the unpredictable chronic mild stress (UCMS) paradigm to examine how chronic stress affects olfactory avoidance behavior and glial cell morphology across multiple olfactory brain regions in male and female mice. UCMS-treated mice showed increased avoidance of aversive odorants in an odorized light/dark box assay, consistent with heightened aversive reactivity to odors following chronic stress. Using immunohistochemistry, we assessed microglial morphology and astrocyte density across six olfactory and limbic brain regions. Chronic stress produced region-specific glial remodeling: astrocyte counts were selectively elevated in the medial amygdala, and microglial process complexity was increased in the anterior olfactory nucleus and anterior piriform cortex. Microglial morphologica...

Aggression may be behaviorally distinguished by reactive or appetitive properties. Here, we use a model of operant aggression administration, in which outbred male CD-1 mice lever press (contingent) or do not lever press (noncontingent) to attack an intruder mouse, to examine behavioral differences in aggression reinforcement. Contingent reinforcement identifies the behavioral and neural basis of appetitive, or rewarding, aggression self-administration, while noncontingent reinforcement isolates reactive, or involuntary, components. Females are not used in this study due to their low propensity to attack. We applied supervised machine-guided behavioral classification and Shapley additive scores (SHAP) to describe differences and similarities in attack behavior features. We find that behavioral sequences of an attack bout are similar whether aggression reinforcement is contingent or noncontingent, though underlying neural mechanisms differ. Fos immunolabeling following operant reinforcement reveals distinct...

Implicit sequence and visuomotor skill learning is important for successful goal-directed behavior in everyday tasks. However, prior research has primarily relied on correlational methods to investigate the underlying neural mechanisms of sequence and visuomotor skill learning. To evaluate the necessary contributions of different motor cortical regions to both types of skill learning, we enrolled 62 neurotypical adults (41 females, 21 males) and delivered spatiotemporally resolved single-pulse transcranial magnetic stimulation (TMS) over either the premotor cortex (PMC) or primary motor cortex (M1) to transiently disrupt activity while participants practiced an implicit motor sequence task. We hypothesized that (1) PMC disruption would preferentially reduce sequence-specific skill acquisition (Experiment 1) and retention (Experiment 2), while (2) M1 disruption would diminish visuomotor skill acquisition and retention but not sequence learning. Our results demonstrated that TMS-based interference over both ...