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 ...

The suprachiasmatic nucleus (SCN) produces diffusible signals sufficient to sustain circadian locomotor rhythms, although the nature of such signals, their targets, and the pathway whereby such signals may travel is unknown. It is possible that the venous portal veins that connect the capillary beds of the SCN to those of the organum vasculosum of the lamina terminalis (OVLT) provide a vascular pathway whereby signals originating in SCN neurons can reach local targets in the OVLT. Given the presence of the blood–brain interface (BBI) within the SCN, it is unclear how diffusible signals originating in SCN neurons might access the capillary vasculature of this nucleus. Estimates of astrocyte coverage of capillary vasculature range widely, from 70 to 100%, and furthermore such coverage can change dynamically. In the present study, we investigated whether three vasoactive peptidergic processes found in the mouse SCN, namely, vasopressin, vasoactive intestinal peptide, and gastrin-releasing peptide, might breac...

Animal learning can be analyzed on two timescales: task acquisition across training sessions and motivation fluctuations within training sessions. How do variations in motor and neurophysiologic activity relate to task performance over these timescales? Here, this question was examined in head-fixed mice performing a whisker-based sensory discrimination task. Male mice were trained for 12–14 daily sessions on a go/no-go task, each lasting ∼1 h to capture spontaneous performance fluctuations over minutes. Simultaneous to task performance, “nonperformance variables” were tracked, including wheel running, pupil size, eyelid aperture, and sensory cortical activity. First, motivation states were defined based on performance tendencies over minutes, leading to three state categories: persistent, disengaged, or attentive. Nonperformance variables were found to predict these states independent of task correctness. Then, when further parsing these states by the go/no-go outcomes of hit, miss, false alarm, or correc...

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 ...

The amount of time previously spent awake or asleep strongly impacts the sleep electroencephalogram (EEG), especially slow waves during non-rapid-eye-movement (NREM) sleep. These effects on the sleep EEG meaningfully interact with age and to a lesser extent developmental disorders such as attention-deficit hyperactivity disorder (ADHD). We aimed to determine whether EEG oscillations during wakefulness were likewise affected by the interaction of sleep and development, using data collected from 163 participants 3-25 years old (62 female). We analyzed age- and sleep-dependent changes in two measures of oscillatory activity (amplitudes and density) and aperiodic activity (offsets and exponents). Finally, we compared wake EEG in children with ADHD (N=58) to neurotypical controls, with habitual good sleep quality required for inclusion. We found that oscillation amplitudes exhibited the same dynamics as sleep slow waves: decreasing with age, decreasing after sleep, and the overnight decrease decreasing with age...

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, 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, crossover training and testing on spike-wave discharges from injured and sham-control rats distinguished a convulsive-seizure phenotype from normal spike-wave discharges. Convolutional neural network mo...

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 (MCAO) 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 (...

Multi-electrode recording of neuronal activity in cultures offer opportunities for understanding how the structure of a network gives rise to function. Neuronal cultures derived from human induced pluripotent stem cells (iPSCs) from male and female individuals are often plated at highly variable cell densities across studies, but its impact on neuronal activity remains poorly understood. We found that properties such as the mean firing rate of the individual cells, the pair-wise correlations between cells, and the entropy of the population all changed significantly with changes in culture density. We used a maximum entropy model to capture the structure of the population activity using only the firing rates and correlations, we found that the model performed best at the highest densities, suggesting that changes in activity reflected differences in structure of interactions between neurons across scales of complexity. Our work thus shows that culture density is an important experimental parameter that impa...

There is considerable interest in cannabinoid-based therapies to treat pain, but activation of the endogenous cannabinoid (endocannabinoid) system can elicit pro- and anti-nociceptive effects. This study tests the hypothesis that the concentration of the endocannabinoid arachidonoylethanolamine (AEA) contributes to whether pro- or anti-nociceptive effects are observed. Experiments were carried out using isolated ganglia from the medicinal leech Hirudo verbana where it is possible to selectively record from nociceptive and non-nociceptive synapses in the central nervous system (CNS). Previous studies using Hirudo have shown that endocannabinoids depress nociceptive (N) synapses and potentiate of non-nociceptive pressure (P) synapses. In this study, exogenously applied AEA produced depression of N synapses and potentiation of P synapses across the same range of concentrations. However, the results differed when using URB597, a drug that raises AEA by inhibiting fatty acid amine hydrolase (FAAH), the enzyme t...