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Cholinergic and noradrenergic neuromodulation of the synaptic transmission from cortical layer 6 of the primary somatosensory cortex to neurons in the posteromedial thalamic nucleus (PoM) was studied using an in vitro slice preparation from young rats. Cholinergic agonist carbachol substantially decreased the amplitudes of consecutive excitatory postsynaptic potentials (EPSPs) evoked by a 20 Hz five pulse train. The decreased amplitude effect was counteracted by a parallel increase of synaptic frequency-dependent facilitation. We found this modulation to be mediated by muscarinic acetylcholine receptors. In the presence of carbachol the amplitudes of the postsynaptic potentials showed a higher trial-to-trial coefficient of variation (CV), which suggested a presynaptic site of action for the modulation. To substantiate this finding, we measured the failure rate of the excitatory postsynaptic currents in PoM cells evoked by "pseudominimal" stimulation of corticothalamic input. A higher failure-rate in the presence of carbachol indicated decreased probability of transmitter release at the synapse. Activation of the noradrenergic modulatory system that was mimicked by application of norepinephrine did not affect the amplitude of the first EPSP evoked in the five-pulse train, but later EPSPs were diminished. This indicated a decrease of the synaptic frequency-dependent facilitation. Treatment with noradrenergic α-2 agonist clonidine, α-1 agonist phenylephrine, or β-receptor agonist isoproterenol showed that the modulation may partly rely on α-2 adrenergic receptors. CV analysis did not suggest a presynaptic action of norepinephrine. We conclude that cholinergic and noradrenergic modulation act as different variable dynamic controls for the corticothalamic mechanism of the frequency-dependent facilitation in PoM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nersisyan, Bekisz, Kublik, Granseth and Wróbel.)

Parvalbumin-positive neurons are the largest class of GABAergic, inhibitory neurons in the central nervous system. In the cortex, these fast-spiking cells provide feedforward and feedback synaptic inhibition onto a diverse set of cell types, including pyramidal cells, other inhibitory interneurons, and themselves. Cortical inhibitory networks broadly, and cortical parvalbumin-expressing interneurons (cPVins) specifically, are crucial for regulating sensory plasticity during both development and adulthood. Here we review the functional properties of cPVins that enable plasticity in the cortex of adult mammals and the influence of cPVins on sensory activity at four spatiotemporal scales. First, cPVins regulate developmental critical periods and adult plasticity through molecular and structural interactions with the extracellular matrix. Second, they activate in precise sequence following feedforward excitation to enforce strict temporal limits in response to the presentation of sensory stimuli. Third, they implement gain control to normalize sensory inputs and compress the dynamic range of output. Fourth, they synchronize broad network activity patterns in response to behavioral events and state changes. Much of the evidence for the contribution of cPVins to plasticity comes from classic models that rely on sensory deprivation methods to probe experience-dependent changes in the brain. We support investigating naturally occurring, adaptive cortical plasticity to study cPVin circuits in an ethologically relevant framework, and discuss recent insights from our work on maternal experience-induced auditory cortical plasticity. [ABSTRACT FROM AUTHOR]

The function of the higher-order sensory thalamus remains unclear. Here, the posterior medial (POm) nucleus of the thalamus was examined by in vivo extracellular recordings in anesthetized rats across a variety of contralateral, ipsilateral, and bilateral whisker sensory patterns. We found that POm was highly sensitive to multiwhisker stimuli involving diverse spatiotemporal interactions. Accurate increases in POm activity were produced during the overlapping time between spatial signals reflecting changes in the spatiotemporal structure of sensory patterns. In addition, our results showed for first time that POm was also able to respond to tactile stimulation of ipsilateral whiskers. This finding challenges the notion that the somatosensory thalamus only computes unilateral stimuli. We found that POm also integrates signals from both whisker pads and described how this integration is generated. Our results showed that ipsilateral activity reached one POm indirectly from the other POm and demonstrated a transmission of sensory activity between both nuclei through a functional POm-POm loop formed by thalamocortical, interhemispheric, and corticothalamic projections. The implication of different cortical areas was investigated revealing that S1 plays a central role in this POm-POm loop. Accordingly, the subcortical and cortical inputs allow POm but not the ventral posteromedial thalamic nucleus (VPM) to have sensory information from both sides of the body. This finding is in agreement with the higher-order nature of POm and can be considered to functionally differentiate and classify these thalamic nuclei. A possible functional role of these higher-order thalamic patterns of integrated activity in brain function is discussed. [ABSTRACT FROM AUTHOR]

Objective: In this study we introduce the use of the current source density (CSD)method as a way to visualize the spatial organization of evoked responses in the rat subthalamic nucleus (STN) at fixed time stamps resulting from motor cortex stimulation. This method offers opportunities to visualize neuronal input and study the relation between the synaptic input and the neural output of neural populations. Approach: Motor cortex evoked local field potentials and unit activity were measured in the subthalamic region, with a 3D measurement grid consisting of 320 measurement points and high spatial resolution. This allowed us to visualize the evoked synaptic input by estimating the current source density (CSD) from the measured local field potentials, using the inverse CSD method. At the same time, the neuronal output of the cells within the grid is assessed by calculating post stimulus time histograms. Main results: The CSD method resulted in clear and distinguishable sources and sinks of the neuronal input activity in the STN after motor cortex stimulation. We showed that the center of the synaptic input of the STN from the motor cortex is located dorsal to the input from globus pallidus. Significance: For the first time we have performed CSD analysis on motor cortex stimulation evoked LFP responses in the rat STN as a proof of principle. Our results suggest that the CSD method can be used to gain new insights into the spatial extent of synaptic pathways in brain structures. [ABSTRACT FROM AUTHOR]

Electrical synapses are a type of cellular membrane junction referred to as gap junctions (GJs). They provide a direct way to exchange ions between coupled cells and have been proposed as a structural basis for fast transmission of electrical potentials between neurons in the brain. For this reason GJs have been regarded as an important component within the neuronal networks that underlie synchronous neuronal activity and field potential oscillations. Initially GJs appeared to play a particularly key role in the generation of high frequency oscillatory patterns in field potentials. In order to assess the scale of neuronal GJs contribution to field potential oscillations in the hippocampal formation, in vivo and in vitro studies are reviewed here. These investigations have shown that blocking the main neuronal GJs, those containing connexin 36 (Cx36-GJs), or knocking out the Cx36 gene affect field potential oscillatory patterns related to awake active behavior {gamma and theta rhythm) but have no effect on high frequency oscillations occurring during silent wake and sleep. Precisely how Cx36-GJs influence population activity of neurons is more complex than previously thought. Analysis of studies on the properties of transmission through GJ channels as well as Cx36-GJs functioning in pairs of coupled neurons provides some explanations of the specific influence of Cx36-GJs on field potential oscillations. It is proposed here that GJ transmission is strongly modulated by the level of neuronal network activity and changing behavioral states. Therefore, contribution of GJs to field potential oscillatory patterns depends on the behavioral state. I propose here a model, based on large body of experimental data gathered in this field by several authors, in which Cx36-GJ transmission especially contributes to oscillations related to active behavior, where it plays a role in filtering and enhancing coherent signals in the network under high-noise conditions. In contrast, oscillations related to silent wake or sleep, especially high frequency oscillations, do not require transmission by neuronal GJs. The reliability of neuronal discharges during those oscillations could be assured by conditions of higher signal-to-noise ratio and some synaptic changes taking place during active behavior. [ABSTRACT FROM AUTHOR]

Here we propose a methodology to analyze volumetric electrical activity of neuronal masses in the somatosensory barrel field ofWistar rats. The key elements of the proposed methodology are a three-dimensional microelectrode array, which was customized by our group to observe extracellular recordings from an extended area of the barrel field, and a novel method for the current source density analysis. By means of this methodology, we were able to localize single barrels from their event-related responses to single whisker deflection. It was also possible to assess the spatiotemporal dynamics of neuronal aggregates in several barrels at the same time with the resolution of single neurons. We used simulations to study the robustness of our methodology to unavoidable physiological noise and electrode configuration. We compared the accuracy to reconstruct neocortical current sources with that obtained with a previous method. This constitutes a type of electrophysiological microscopy with high spatial and temporal resolution, which could change the way we analyze the activity of cortical neurons in the future. [ABSTRACT FROM AUTHOR]