Insight into the cellular and circuit mechanisms underlying development of temporal lobe epilepsy will provide a foundation for improved therapies. We studied a model in which an episode of prolonged seizures is followed by recovery lasting two weeks before emergence of spontaneous recurrent seizures. We focused on the interval between the prolonged seizures and the late onset recurrent seizures. We investigated the hippocampal mossy fiber CA3 pyramidal cell microcircuit in models spanning in vitro , in vivo , and ex vivo preparations. Expression of channelrhodopsin-2 in the dentate granule cells of DGC ChR mice enabled the selective activation of mossy fiber axons. In vivo studies revealed marked potentiation of mossy fiber evoked field potentials in hippocampal CA3 beginning within hours following seizures, a potentiation which persisted at least seven days. Stimulation of mossy fibers in hippocampal slices in vitro using patterns of activity mimicking seizures induced LTP not only of the monosynaptic EP...

The precise location of the human female genital representation field in the primary somatosensory cortex (S1) is controversial and its capacity for use-associated structural variation as a function of sexual behavior remains unknown. We used an fMRI-compatible sensory-tactile stimulation paradigm to functionally map the location of the female genital representation field in 20 adult women. Neural response to tactile stimulation of the clitoral region (versus right hand) identified individually-diverse focal bilateral activations in dorsolateral areas of S1 (BA1-BA3) in alignment with anatomical location. We next used cortical surface analyses to assess structural thickness across the 10 individually most activated vertices per hemisphere for each woman. We show that frequency of sexual intercourse within 12 months is correlated with structural thickness of the individually-mapped left genital field. Our results provide a precise functional localization of the female genital field and provide support for u...

The arcuate nucleus (ArcN) is an integrative hub for the regulation of energy balance, reproduction, and arterial pressure (AP), all of which are influenced by Angiotensin II (AngII); however, the cellular mechanisms and downstream neurocircuitry are unclear. Here we show that ArcN AngII increases AP in female rats via two phases, both of which are mediated via activation of AngII type 1 receptors (AT1aR): initial vasopressin-induced vasoconstriction, followed by slowly developing increases in sympathetic nerve activity (SNA) and heart rate (HR). In male rats, ArcN AngII evoked a similarly slow increase in SNA, but the initial pressor response was variable. In females, the effects of ArcN AngII varied during the estrus cycle, with significant increases in SNA, HR, and AP occurring during diestrus and estrus, but only increased AP during proestrus. Pregnancy markedly increased the expression of AT1aR in the ArcN with parallel substantial AngII-induced increases in SNA and MAP. In both sexes, the sympathoexc...

Activity of dorsal raphe neurons is controlled by noradrenaline afferents. In this brain region, noradrenaline activates Gαq-coupled α1-adrenergic receptors (α1-AR), causing action potential firing and serotonin release. In vitro , electrical stimulation elicits vesicular noradrenaline release and subsequent activation of α1-AR to produce an excitatory postsynaptic current (α1-AR-EPSC). The duration of the α1-AR-EPSC (∼27 s) is much longer than that of most other synaptic currents, but the factors that govern the spatiotemporal dynamics of α1-AR are poorly understood. Using an acute brain slice preparation from adult male and female mice and electrophysiological recordings from dorsal raphe neurons, we found that the time-course of the α1-AR-EPSC was slow, but highly consistent within individual serotonin neurons. The amount of noradrenaline released influenced the amplitude of the α1-AR-EPSC without altering the time constant of decay suggesting that once released, extracellular noradrenaline was cleared ...

Response nonlinearities are ubiquitous throughout the brain, especially within sensory cortices where changes in stimulus intensity typically produce compressed responses. Although this relationship is well-established in electrophysiological measurements, it remains controversial whether the same nonlinearities hold for population-based measurements obtained with human fMRI. We propose that these purported disparities are not contingent upon measurement type, and are instead largely dependent upon the visual system state at the time of interrogation. We show that deploying a contrast adaptation paradigm permits reliable measurements of saturating sigmoidal contrast response functions (10 participants, 7 female). When not controlling the adaptation state, our results coincide with previous fMRI studies, yielding non-saturating, largely linear contrast responses. These findings highlight the important role of adaptation in manifesting measurable nonlinear responses within human visual cortex, reconciling di...

Peripheral nerves are divided into multiple branches leading to divergent synaptic targets. This poses a remarkable challenge for regenerating axons as they select their original trajectory at nerve branch-points. Despite implications for functional regeneration, the molecular mechanisms underlying target selectivity are not well characterized. Danio Rerio (zebrafish) motor nerves are composed of a ventral and a dorsal branch that diverge at a choice-point, and we have previously shown that regenerating axons faithfully select their original branch and targets. Here we identify Robo2 as a key regulator of target-selective regeneration (sex of experimental subjects unknown). We demonstrate that Robo2 function in regenerating axons is required and sufficient to drive target-selective regeneration, and that Robo2 acts in response to glia located precisely where regenerating axons select the branch-specific trajectory to prevent and correct axonal errors. Combined our results reveal a glia derived mechanism th...

Background : Noise introduced in the human nervous system from cellular to systems levels can have a major impact on signal processing. Using transcranial stimulation, electrical noise can be added to cortical circuits to modulate neuronal activity and enhance function in the healthy brain and in neurological patients. Transcranial random noise stimulation (tRNS) is a promising technique that is less well understood than other non-invasive neuromodulatory methods. Objective: The aim of the present scoping review is to collate published evidence on the effects of electrical noise at the cellular, systems, and behavioural levels, and discuss how this emerging method might be harnessed to augment perceptual and motor functioning of the human nervous system. Design: Online databases were used to identify papers published 2008–2021 using tRNS in humans, from which we identified 70 publications focusing on sensory and motor function. Additionally, we interpret the existing evidence by referring to articles inv...

Exposure of the fetus to alcohol (ethanol) via maternal consumption during pregnancy can result in fetal alcohol spectrum disorders (FASD), hallmarked by long-term physical, behavioral, and intellectual abnormalities. In our preclinical mouse model of FASD, prenatal ethanol exposure disrupts tangential migration of corticopetal GABAergic interneurons in the embryonic medial prefrontal cortex (mPFC). We postulated that ethanol perturbed the normal pattern of tangential migration via enhancing GABAA receptor-mediated membrane depolarization that prevails during embryonic development in GABAergic cortical interneurons. However, beyond this, our understanding of the underlying mechanisms is incomplete. Here, we tested the hypothesis that the ethanol-enhanced depolarization triggers downstream an increase in high-voltage activated nifedipine-sensitive L-type calcium channel (LTCC) activity, and provide evidence implicating calcium dynamics in the signaling scheme underlying the migration of embryonic GABAergic ...