Response adaptation in barrel cortical neurons facilitates stimulus detection during rhythmic whisker stimulation in anesthetized mice

Rodents use rhythmic whisker movements at frequencies between 4 and 12 Hz to sense the environment that will be disturbed when the animal touches an object. The aim of this work is to study the response adaptation to rhythmic whisker stimulation trains at 4 Hz in the barrel cortex and the sensitivity of cortical neurons to changes in the timing of the stimulation pattern. Longitudinal arrays of four iridium oxide electrodes were used to obtain single-unit recordings in supragranular, granular, and infragranular neurons in urethane anesthetized mice. The stimulation protocol consisted in a stimulation train of three air puffs (20 ms duration each) in which the time interval between the first and the third stimuli was fixed (500 ms) and the time interval between the first and the second stimuli changed (regular: 250 ms; “accelerando”: 375 ms; or “decelerando” stimulation train: 125 ms interval). Cortical neurons adapted strongly their response to regular stimulation trains. Response adaptation was reduced when accelerando or decelerando stimulation trains were applied. This facilitation of the shifted stimulus was mediated by activation of NMDA receptors because the effect was blocked by AP5. The facilitation was not observed in thalamic nuclei. Facilitation increased during periods of EEG activation induced by systemic application of IGF-I, probably by activation of NMDA receptors, as well. We suggest that response adaptation is the outcome of an intrinsic cortical information processing aimed at contributing to improve the detection of “unexpected” stimuli that disturbed the rhythmic behavior of exploratio

Modulation of specific sensory cortical areas by segregated basal forebrain cholinergic neurons demonstrated by neuronal tracing and optogenetic stimulation in mice

Neocortical cholinergic activity plays a fundamental role in sensory processing and cognitive functions. Previous results have suggested a refined anatomical and functional topographical organization of basal forebrain (BF) projections that may control cortical sensory processing in a specific manner. We have used retrograde anatomical procedures to demonstrate the existence of specific neuronal groups in the BF involved in the control of specific sensory cortices. Fluoro-Gold (FlGo) and Fast Blue (FB) fluorescent retrograde tracers were deposited into the primary somatosensory (S1) and primary auditory (A1) cortices in mice. Our results revealed that the BF is a heterogeneous area in which neurons projecting to different cortical areas are segregated into different neuronal groups. Most of the neurons located in the horizontal limb of the diagonal band of Broca (HDB) projected to the S1 cortex, indicating that this area is specialized in the sensory processing of tactile stimuli. However, the nucleus basalis magnocellularis (B) nucleus shows a similar number of cells projecting to the S1 as to the A1 cortices. In addition, we analyzed the cholinergic effects on the S1 and A1 cortical sensory responses by optogenetic stimulation of the BF neurons in urethane-anesthetized transgenic mice. We used transgenic mice expressing the light-activated cation channel, channelrhodopsin-2, tagged with a fluorescent protein (ChR2-YFP) under the control of the choline-acetyl transferase promoter (ChAT). Cortical evoked potentials were induced by whisker deflections or by auditory clicks. According to the anatomical results, optogenetic HDB stimulation induced more extensive facilitation of tactile evoked potentials in S1 than auditory evoked potentials in A1, while optogenetic stimulation of the B nucleus facilitated either tactile or auditory evoked potentials equally. Consequently, our results suggest that cholinergic projections to the cortex are organized into segregated pools of neurons that may modulate specific cortical areas.This work was supported by a Grant from Ministerio de Economia y Competitividad ( BFU2012–36107

Bidirectional hebbian plasticity induced by low-frequency stimulationin basal dendrites of rat barrel cortex layer 5 pyramidal neurons

According to Hebb’s original hypothesis (Hebb,1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic in put causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca2+ spike and Ca2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor informationWork supported by “Ministerio de Ciencia y Tecnología y Ministerio de Ciencia e Innovación” grants (BFU2005-07486, BFU2008-03488, SAF2009-10339, BFU2011-23522, BFU2012-36107, BFU2013-43668-P and BFU2016-80802-P) and a “Comunidad Autónoma de Madrid” (GR/SAL/0877/2004) grant. Dr .D. Fernández de Sevilla was a post doctoral fellow at the “Instituto Cajal,” funded by GR/SAL/0877/2004 and a “Ministerio de Ciencia and Tecnología” grant (BFU2005-07486).He was subsequently supported by a Ramón y Cajal Contract and is now a Professor at the “Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid.” Dr. Andrea Diez was a doctoral fellow funded by the BFU2011-23522 grant and is now a post doctoral fellow funded by “Ministerio de Ciencia e Innovación” grant (BFU2013- 43741-P) at the “Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid.” N. Barros-Zulaica was a doctoral fellow funded by the BFU2012-36107 gran

Corrigendum: Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons

Peer reviewedPeer Reviewe

Control of somatosensory cortical processing by thalamic posterior medial nucleus: A new role of thalamus in cortical function

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Current knowledge of thalamocortical interaction comes mainly from studying lemniscal thalamic systems. Less is known about paralemniscal thalamic nuclei function. In the vibrissae system, the posterior medial nucleus (POm) is the corresponding paralemniscal nucleus. POm neurons project to L1 and L5A of the primary somatosensory cortex (S1) in the rat brain. It is known that L1 modifies sensory-evoked responses through control of intracortical excitability suggesting that L1 exerts an influence on whisker responses. Therefore, thalamocortical pathways targeting L1 could modulate cortical firing. Here, using a combination of electrophysiology and pharmacology in vivo, we have sought to determine how POm influences cortical processing. In our experiments, single unit recordings performed in urethane- anesthetized rats showed that POm imposes precise control on the magnitude and duration of supra- and infragranular barrel cortex whisker responses. Our findings demonstrated that L1 inputs from POm imposed a time and intensity dependent regulation on cortical sensory processing. Moreover, we found that blocking L1 GABAergic inhibition or blocking P/Q-type Ca2+ channels in L1 prevents POm adjustment of whisker responses in the barrel cortex. Additionally, we found that POm was also controlling the sensory processing in S2 and this regulation was modulated by corticofugal activity from L5 in S1. Taken together, our data demonstrate the determinant role exerted by the POm in the adjustment of somatosensory cortical processing and in the regulation of cortical processing between S1 and S2. We propose that this adjustment could be a thalamocortical gain regulation mechanism also present in the processing of information between cortical areas.This work was supported by a grant from Ministerio de Economia y Competitividad (BFU2012- 36107

POm E-stimulation before whisker stimulus does not decrease cortical response magnitude and duration when PTX is applied in L1.

<p>(A) Percentage change in mean response magnitude by POm E-stimulation before (black) and after PTX application (grey). POm E-stimulation did not decrease cortical response magnitude when GABAergic inhibitory transmission in L1 was blocked. (B) PTX application in L1 increased whisker offset response latency in infra- and supragranular layers. POm E-stimulation before whisker stimulus did not decrease cortical response duration when PTX was applied in L1. Control (orange) and POm E-stimulation (blue) conditions are shown.</p

Muscimol-induced inactivation of the VPM.

<p>Inactivating VPM decreased responses in infra- and supragranular layers of S1. (A) Raster plots and PSTHs are shown for a supragranular sample neuron before (orange) and after (brown) VPM inactivation. (B) Mean response magnitude change (%) evoked by VPM inactivation. In both layers, spikes of sensory responses were strongly abolished after VPM inactivation by muscimol.</p

POm responses lasted the duration of the whisker stimulus.

<p>Raster plots and PSTHs showing sustained multiunit POm responses evoked by different stimulus duration (top: 20 ms, middle: 80 ms and bottom: 200 ms). Air puff duration is indicated by horizontal orange lines.</p

POm E-stimulation before whisker stimulus does not decrease cortical response magnitude and duration when AGA is applied in L1.

<p>(A) Percentage change in mean response magnitude by POm E-stimulation before (black) and after AGA application (grey). POm E-stimulation before each stimulus (500 ms) did not decrease cortical responses when P/Q-type voltage-gated calcium channels were blocked. (B) AGA application in L1 increased whisker offset response latency in infra- and supragranular layers. POm E-stimulation did not decrease cortical response duration when P/Q-type voltage-gated calcium channels were blocked. Control (orange) and POm E-stimulation (blue) conditions are shown.</p

L1 E-stimulation before sensory stimulus modulates cortical responses.

<p>(A) Schematic diagram indicating the experimental manipulation of the barrel cortex L1. (B) Mean response magnitude variation (%) by L1 E-stimulation is quantified in this Fig Magnitude reduction was more prevalent in the second component of the response in both layers. In infragranular layers, in the first component we did not find a significant decrease of spikes. However, spikes in the second component were decreased strongly by L1 E-stimulation. In supragranular layers, in both components we found a significant reduction of spikes.</p