Presynaptic adenosine receptor-mediated regulation of diverse thalamocortical short-term plasticity in the mouse whisker pathway

Short-term synaptic plasticity (STP) sets the sensitivity of a synapse to incoming activity and determines the temporal patterns that it best transmits. In “driver” thalamocortical (TC) synaptic populations, STP is dominated by depression during stimulation from rest. However, during ongoing stimulation, lemniscal TC connections onto layer 4 neurons in mouse barrel cortex express variable STP. Each synapse responds to input trains with a distinct pattern of depression or facilitation around its mean steady-state response. As a result, in common with other synaptic populations, lemniscal TC synapses express diverse rather than uniform dynamics, allowing for a rich representation of temporally varying stimuli. Here, we show that this STP diversity is regulated presynaptically. Presynaptic adenosine receptors of the A1R type, but not kainate receptors (KARs), modulate STP behavior. Blocking the receptors does not eliminate diversity, indicating that diversity is related to heterogeneous expression of multiple mechanisms in the pathway from presynaptic calcium influx to neurotransmitter release

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

A novel role of dendritic gap junction and mechanisms underlying its interaction with thalamocortical conductance in fast spiking inhibitory neurons

<p>Abstract</p> <p>Background</p> <p>Little is known about the roles of dendritic gap junctions (GJs) of inhibitory interneurons in modulating temporal properties of sensory induced responses in sensory cortices. Electrophysiological dual patch-clamp recording and computational simulation methods were used in combination to examine a novel role of GJs in sensory mediated feed-forward inhibitory responses in barrel cortex layer IV and its underlying mechanisms.</p> <p>Results</p> <p>Under physiological conditions, excitatory post-junctional potentials (EPJPs) interact with thalamocortical (TC) inputs within an unprecedented few milliseconds (i.e. over 200 Hz) to enhance the firing probability and synchrony of coupled fast-spiking (FS) cells. Dendritic GJ coupling allows fourfold increase in synchrony and a significant enhancement in spike transmission efficacy in excitatory spiny stellate cells. The model revealed the following novel mechanisms: <b><it>1) </it></b>rapid capacitive current (I_cap) underlies the activation of voltage-gated sodium channels; <b><it>2) </it></b>there was less than 2 milliseconds in which the I_capunderlying TC input and EPJP was coupled effectively; <b><it>3) </it></b>cells with dendritic GJs had larger input conductance and smaller membrane response to weaker inputs; <b><it>4) </it></b>synchrony in inhibitory networks by GJ coupling leads to reduced sporadic lateral inhibition and increased TC transmission efficacy.</p> <p>Conclusion</p> <p>Dendritic GJs of neocortical inhibitory networks can have very powerful effects in modulating the strength and the temporal properties of sensory induced feed-forward inhibitory and excitatory responses at a very high frequency band (>200 Hz). Rapid capacitive currents are identified as main mechanisms underlying interaction between two transient synaptic conductances.</p

Modelling fast forms of visual neural plasticity using a modified second-order motion energy model

The Adelson-Bergen motion energy sensor is well established as the leading model of low-level visual motion sensing in human vision. However, the standard model cannot predict adaptation effects in motion perception. A previous paper Pavan et al.(Journal of Vision 10:1-17, 2013) presented an extension to the model which uses a first-order RC gain-control circuit (leaky integrator) to implement adaptation effects which can span many seconds, and showed that the extended model's output is consistent with psychophysical data on the classic motion after-effect. Recent psychophysical research has reported adaptation over much shorter time periods, spanning just a few hundred milliseconds. The present paper further extends the sensor model to implement rapid adaptation, by adding a second-order RC circuit which causes the sensor to require a finite amount of time to react to a sudden change in stimulation. The output of the new sensor accounts accurately for psychophysical data on rapid forms of facilitation (rapid visual motion priming, rVMP) and suppression (rapid motion after-effect, rMAE). Changes in natural scene content occur over multiple time scales, and multi-stage leaky integrators of the kind proposed here offer a computational scheme for modelling adaptation over multiple time scales. © 2014 Springer Science+Business Media New York

Parallel Thalamic Pathways for Whisking and Touch Signals in the Rat

In active sensation, sensory information is acquired via movements of sensory organs; rats move their whiskers repetitively to scan the environment, thus detecting, localizing, and identifying objects. Sensory information, in turn, affects future motor movements. How this motor-sensory-motor functional loop is implemented across anatomical loops of the whisker system is not yet known. While inducing artificial whisking in anesthetized rats, we recorded the activity of individual neurons from three thalamic nuclei of the whisker system, each belonging to a different major afferent pathway: paralemniscal, extralemniscal (a recently discovered pathway), or lemniscal. We found that different sensory signals related to active touch are conveyed separately via the thalamus by these three parallel afferent pathways. The paralemniscal pathway conveys sensor motion (whisking) signals, the extralemniscal conveys contact (touch) signals, and the lemniscal pathway conveys combined whisking–touch signals. This functional segregation of anatomical pathways raises the possibility that different sensory-motor processes, such as those related to motion control, object localization, and object identification, are implemented along different motor-sensory-motor loops

Stimulus Dependence of Barrel Cortex Directional Selectivity

Neurons throughout the rat vibrissa somatosensory pathway are sensitive to the angular direction of whisker movement. Could this sensitivity help rats discriminate stimuli? Here we use a simple computational model of cortical neurons to analyze the robustness of directional selectivity. In the model, directional preference emerges from tuning of synaptic conductance amplitude and latency, as in recent experimental findings. We find that directional selectivity during stimulation with random deflection sequences is strongly dependent on the mean deflection frequency: Selectivity is weakened at high frequencies even when each individual deflection evokes strong directional tuning. This variability of directional selectivity is due to generic properties of synaptic integration by the neuronal membrane, and is therefore likely to hold under very general physiological conditions. Our results suggest that directional selectivity depends on stimulus context. It may participate in tasks involving brief whisker contact, such as detection of object position, but is likely to be weakened in tasks involving sustained whisker exploration (e.g., texture discrimination)

Shifts in Coding Properties and Maintenance of Information Transmission during Adaptation in Barrel Cortex

Neuronal responses to ongoing stimulation in many systems change over time, or “adapt.” Despite the ubiquity of adaptation, its effects on the stimulus information carried by neurons are often unknown. Here we examine how adaptation affects sensory coding in barrel cortex. We used spike-triggered covariance analysis of single-neuron responses to continuous, rapidly varying vibrissa motion stimuli, recorded in anesthetized rats. Changes in stimulus statistics induced spike rate adaptation over hundreds of milliseconds. Vibrissa motion encoding changed with adaptation as follows. In every neuron that showed rate adaptation, the input–output tuning function scaled with the changes in stimulus distribution, allowing the neurons to maintain the quantity of information conveyed about stimulus features. A single neuron that did not show rate adaptation also lacked input–output rescaling and did not maintain information across changes in stimulus statistics. Therefore, in barrel cortex, rate adaptation occurs on a slow timescale relative to the features driving spikes and is associated with gain rescaling matched to the stimulus distribution. Our results suggest that adaptation enhances tactile representations in primary somatosensory cortex, where they could directly influence perceptual decisions

Short-term synaptic plasticity in the nociceptive thalamic-anterior cingulate pathway

<p>Abstract</p> <p>Background</p> <p>Although the mechanisms of short- and long-term potentiation of nociceptive-evoked responses are well known in the spinal cord, including central sensitization, there has been a growing body of information on such events in the cerebral cortex. In view of the importance of anterior cingulate cortex (ACC) in chronic pain conditions, this review considers neuronal plasticities in the thalamocingulate pathway that may be the earliest changes associated with such syndromes.</p> <p>Results</p> <p>A single nociceptive electrical stimulus to the sciatic nerve induced a prominent sink current in the layer II/III of the ACC <it>in vivo</it>, while high frequency stimulation potentiated the response of this current. Paired-pulse facilitation by electrical stimulation of midline, mediodorsal and intralaminar thalamic nuclei (MITN) suggesting that the MITN projection to ACC mediates the nociceptive short-term plasticity. The short-term synaptic plasticities were evaluated for different inputs <it>in vitro </it>where the medial thalamic and contralateral corpus callosum afferents were compared. Stimulation of the mediodorsal afferent evoked a stronger short-term synaptic plasticity and effectively transferred the bursting thalamic activity to cingulate cortex that was not true for contralateral stimulation. This short-term enhancement of synaptic transmission was mediated by polysynaptic pathways and NMDA receptors. Layer II/III neurons of the ACC express a short-term plasticity that involves glutamate and presynaptic calcium influx and is an important mechanism of the short-term plasticity.</p> <p>Conclusion</p> <p>The potentiation of ACC neuronal activity induced by thalamic bursting suggest that short-term synaptic plasticities enable the processing of nociceptive information from the medial thalamus and this temporal response variability is particularly important in pain because temporal maintenance of the response supports cortical integration and memory formation related to noxious events. Moreover, these modifications of cingulate synapses appear to regulate afferent signals that may be important to the transition from acute to chronic pain conditions associated with persistent peripheral noxious stimulation. Enhanced and maintained nociceptive activities in cingulate cortex, therefore, can become adverse and it will be important to learn how to regulate such changes in thalamic firing patterns that transmit nociceptive information to ACC in early stages of chronic pain.</p