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...

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 ...

Acquiring new memories is a multi-stage process. Numerous studies have convincingly demonstrated that initially acquired memories are labile, and only stabilized by later consolidation processes. These multiple phases of memory formation are known to involve modification of both cellular excitability and synaptic connectivity, which in turn change neuronal activity at both the single neuron and ensemble levels. However, the specific mapping between the known phases of memory and the changes in neuronal activity at different organizational levels – the single-neuron, population representations, and ensemble state dynamics – remains unknown. Here we address this issue in the context of conditioned taste aversion learning by continuously tracking gustatory cortex (GC) neuronal taste responses in alert male and female rats during the 24 hours following a taste-malaise pairing. We found that the progression of activity changes depends on the neuronal organizational level: whereas the population response changed...

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...

Aging is often associated with cognitive decline and recurrent cellular and molecular impairments. While life-long caloric restriction (CR) may delay age-related cognitive deterioration as well as the onset of neurological disease, recent studies suggest that late-onset, short-term intermittent fasting (IF), may show comparable beneficial effects as those of life-long CR to improve brain health. We used a new optogenetic aging model to study the effects of late-onset (>18 months), short-term (4-6 weeks) IF on age-related changes in GABAergic synaptic transmission, intracellular calcium (Ca2+) buffering and cognitive status. We utilized male mice from a bacterial artificial chromosome (BAC) transgenic mouse line with stable expression of the channelrhodopsin-2 (ChR2) variant H134R [VGAT-ChR2(H134R)-EYFP] in a reduced synaptic preparation that allows for specific optogenetic light stimulation on GABAergic synaptic terminals across aging. We performed quantal analysis using the method of failures in this mode...

Years of basic neuroscience on the modulation of the small circuits found in the crustacean stomatogastric ganglion have led us to study the effects of temperature on the motor patterns produced by the stomatogastric ganglion. While the impetus for this work was the study of individual variability in the parameters determining intrinsic and synaptic conductances, we are confronting substantial fluctuations in the stability of the networks to extreme temperature; these may correlate with changes in ocean temperature. Interestingly, when studied under control conditions, these wild-caught animals appear to be unchanged, but it is only when challenged by extreme temperatures that we reveal the consequences of warming oceans.