Synchronization in the gamma band (25–150 Hz) is mediated by PV+ inhibitory interneurons, and evidence is accumulating for the essential role of gamma oscillations in cognition. Oscillations can arise in inhibitory networks via synaptic interactions between individual oscillatory neurons (mean-driven) or via strong recurrent inhibition that destabilizes the stationary background firing rate in the fluctuation-driven balanced state, causing an oscillation in the population firing rate. Previous theoretical work focused on model neurons with Hodgkin's Type 1 excitability (integrators) connected by current-based synapses. Here we show that networks comprised of simple Type 2 oscillators (resonators) exhibit a supercritical Hopf bifurcation between synchrony and asynchrony and a gradual transition via cycle skipping from coupled oscillators to stochastic population oscillator (SPO), as previously shown for Type 1. We extended our analysis to homogeneous networks with conductance rather than current based synap...

Brain-derived neurotrophic factor (BDNF) is important in the development and maintenance of neurons and their plasticity. Hippocampal BDNF has been implicated in Alzheimer’s disease (AD) because hippocampal levels in AD patients and AD animal models are often downregulated, suggesting that reduced BDNF contributes to AD. However, the location where hippocampal BDNF protein is most highly expressed, the mossy fiber (MF) axons of dentate gyrus granule cells (GCs), has been understudied, and not in controlled conditions. Therefore, we evaluated MF BDNF protein in the Tg2576 mouse model of AD. Tg2576 and wild-type (WT) mice of both sexes were examined at 2–3 months of age, when amyloid-β (Aβ) is present in neurons but plaques are absent, and 11–20 months of age, after plaque accumulation. As shown previously, WT mice exhibited high levels of MF BDNF protein. Interestingly, there was no significant decline with age in either the genotype or sex. Notably, MF BDNF protein was correlated with GC ΔFosB, a transcrip...

The transition from acute to chronic pain involves maladaptive plasticity in central nociceptive pathways. Growing evidence suggests that changes within the parabrachial nucleus (PBN), an important component of the spino–parabrachio–amygdaloid pain pathway, are key contributors to the development and maintenance of chronic pain. In animal models of chronic pain, PBN neurons become sensitive to normally innocuous stimuli and responses to noxious stimuli become amplified and more often produce afterdischarges that outlast the stimulus. Using ex vivo slice electrophysiology and two mouse models of neuropathic pain, sciatic cuff and chronic constriction of the infraorbital nerve (CCI-ION), we find that changes in the firing properties of PBN neurons and a shift in inhibitory synaptic transmission may underlie this phenomenon. Compared to PBN neurons from shams, a larger proportion of PBN neurons from mice with a sciatic cuff were spontaneously active at rest, and these same neurons showed increased excitabilit...

Spontaneous eye blinking is gaining popularity as a proxy for higher cognitive functions, as it is readily modulated by both environmental demands and internal processes. Prior studies were impoverished in sample size, sex representation, and age distribution, making it difficult to establish a complete picture of the behavior. Here we present eye-tracking data from a large cohort of normative participants ( n  = 604; 393 F; aged 5–93 years) performing two tasks: one with structured, discrete trials (interleaved pro-/anti-saccade task, IPAST) and one with a less structured, continuous organization in which participants watch movies (free-viewing; FV). Sex- and age-based analyses revealed that females had higher blink rates between the ages of 22 and 58 years in the IPAST and 22 and 34 years in FV. We derived a continuous measure of blink probability to reveal behavioral changes driven by stimulus appearance in both paradigms. In the IPAST, blinks were suppressed near stimulus appearance, particularly on co...

Currently there are numerous methods to evaluate peripheral nerve stimulation interfaces in rats, with stimulation-evoked ankle torque being one of the most prominent. Commercial rat ankle torque measurement systems and custom one-off solutions have been published in the literature. However, commercial systems are proprietary and costly and do not allow for customization. One-off lab-built systems have required specialized machining expertise, and building plans have previously not been made easily accessible. Here, detailed building plans are provided for a low-cost, open-source, and basic ankle torque measurement system from which additional customization can be made. A hindlimb stabilization apparatus was developed to secure and stabilize a rat's hindlimb, while allowing for simultaneous ankle-isometric torque and lower limb muscle electromyography (EMG). The design was composed mainly of adjustable 3D-printed components to accommodate anatomical differences between rat hindlimbs. Additionally, construc...

In critically ill newborns, exposure to hypercapnia (HC) is common and often accepted in neonatal intensive care units to prevent severe lung injury. However, as a “safe” range of arterial partial pressure of carbon dioxide levels in neonates has not been established, the potential impact of HC on the neurodevelopmental outcomes in these newborns remains a matter of concern. Here, in a newborn Yorkshire piglet model of either sex, we show that acute exposure to HC induced persistent cortical neuronal injury, associated cognitive and learning deficits, and long-term suppression of cortical electroencephalogram frequencies. HC induced a transient energy failure in cortical neurons, a persistent dysregulation of calcium-dependent proapoptotic signaling in the cerebral cortex, and activation of the apoptotic cascade, leading to nuclear deoxyribonucleic acid fragmentation. While neither 1 h of HC nor the rapid normalization of HC was associated with changes in cortical bioenergetics, rapid resuscitation resulte...

The temporal dynamics within the semantic brain network and its dependence on stimulus and task parameters are still not well understood. Here, we addressed this by decoding task as well as stimulus information from source-estimated EEG/MEG human data. We presented the same visual word stimuli in a lexical decision (LD) and three semantic decision (SD) tasks. The meanings of the presented words varied across five semantic categories. Source space decoding was applied over time in five ROIs in the left hemisphere (anterior and posterior temporal lobe, inferior frontal gyrus, primary visual areas, and angular gyrus) and one in the right hemisphere (anterior temporal lobe). Task decoding produced sustained significant effects in all ROIs from 50 to 100 ms, both when categorizing tasks with different semantic demands (LD-SD) as well as for similar semantic tasks (SD-SD). In contrast, a semantic word category could only be decoded in lATL, rATL, PTC, and IFG, between 250 and 500 ms. Furthermore, we compared two...

Synaptic plasticity is important for learning and memory formation; it describes the strengthening or weakening of connections between synapses. The postsynaptic part of excitatory synapses resides in dendritic spines, which are small protrusions on the dendrites. One of the key features of synaptic plasticity is its correlation with the size of these spines. A long-lasting synaptic strength increase [long-term potentiation (LTP)] is only possible through the reconfiguration of the actin spine cytoskeleton. Here, we develop an experimentally informed three-dimensional computational model in a moving boundary framework to investigate this reconfiguration. Our model describes the reactions between actin and actin-binding proteins leading to the cytoskeleton remodeling and their effect on the spine membrane shape to examine the spine enlargement upon LTP. Moreover, we find that the incorporation of perisynaptic elements enhances spine enlargement upon LTP, exhibiting the importance of accounting for these ele...

Parkinson's disease (PD) patients harbor seeding-competent α-synuclein (α-syn) in their cerebrospinal fluid (CSF), which is mainly produced by the choroid plexus (ChP). Nonetheless, little is known about the role of the CSF and the ChP in PD pathogenesis. To address this question, we used an intracerebroventricular (icv) injection mouse model to assess CSF α-syn spreading and its short- and long-term consequences on the brain. Hereby, we made use of seeding-competent, recombinant α-syn preformed fibrils (PFF) that are known to induce aggregation and subsequent spreading of endogenous α-syn in stereotactic tissue injection models. Here, we show that icv-injected PFF, but not monomers (Mono), are rapidly removed from the CSF by interaction with the ChP. Additionally, shortly after icv injection both Mono and PFF were detected in the olfactory bulb and striatum. This spreading was associated with increased inflammation and complement activation in these tissues as well as leakage of the blood–CSF barrier. Des...

The type I transmembrane protein BT-IgSF is predominantly localized in the brain and testes. It belongs to the coxsackievirus and adenovirus receptor subgroup of Ig cell adhesion proteins, which are hypothesized to regulate connexin expression or localization. Here, we studied the putative link between BT-IgSF and connexins in astrocytes, ependymal cells, and neurons of the mouse. Global knock-out of BT-IgSF caused an increase in the clustering of connexin43 (Gja1), but not of connexin30 (Gjb6), on astrocytes and ependymal cells. Additionally, knock-out animals displayed reduced expression levels of connexin43 protein in the cortex and hippocampus. Importantly, analysis of biocytin spread in hippocampal or cortical slices from mature mice of either sex revealed a decrease in astrocytic cell–cell coupling in the absence of BT-IgSF. Blocking either protein biosynthesis or proteolysis showed that the lysosomal pathway increased connexin43 degradation in astrocytes. Localization of connexin43 in subcellular co...