The Effects of NMDA Receptor Blockade on Sensory-Evoked Responses in Superficial Layers of the Rat Barrel Cortex.

Julia Lebedeva,Gulshat Burkhanova,Kseniya Chernova,Roustem Khazipov,Andrey Zakharov

doi:10.3389/fncel.2019.00259

Abstract

Transmission of excitation from L4 to L2/3 is a part of a canonical circuit of cortical sensory signal processing. While synapses from L4 to L2/3 are mediated by both AMPA and NMDA glutamate receptors, previous studies suggested that sensory-evoked excitation of neurons in supragranular layers is almost entirely mediated by NMDA receptors. Here, we readdressed this question using extracellular recordings of sensory-evoked potentials (SEPs) and multiple unit activity (MUA) in the rat barrel cortex. We found that blockade of NMDA receptors using the selective antagonist dAPV profoundly inhibited the late part of L2/3 SEP, the associated sink, and MUA response but did not affect its initial part. Our results indicate that both non-NMDA and NMDA receptors are involved in sensory signal transmission from L4 to L2/3. While non-NMDA receptors mediate fast transmission of sensory signals, NMDA-Rs are importantly involved in the generation of the late phase of the sensory-evoked response in supragranular layers.

Highlights

The canonical circuit of signal processing in the sensory cortex involves thalamus driven activation of L4 neurons followed by a transfer of excitation from L4 to L2/3 (Gilbert and Wiesel, 1979; Petersen, 2007; Feldmeyer et al, 2013)
In the present study we explored the effects of blockade of cortical NMDA receptors using epipial application of the selective NMDA receptor antagonist dAPV on principal whisker (PW) – evoked responses in L2/3 of a cortical barrel column
DAPV reduced the peak sensory-evoked potentials (SEPs) amplitude from 621 ± 43 μV to 469 ± 38 μV (p = 0.002) and reduced the SEP peak delay after the stimulus onset from 14.3 ± 0.5 ms to 12.7 ± 0.7 ms (p = 0.008). dAPV profoundly inhibited the late part of the SEP with the maximal level of inhibition observed within a time window from 20 to 60 ms after the stimulus

Summary

Introduction

The canonical circuit of signal processing in the sensory cortex involves thalamus driven activation of L4 neurons followed by a transfer of excitation from L4 to L2/3 (Gilbert and Wiesel, 1979; Petersen, 2007; Feldmeyer et al, 2013). Experimental data and the results of modeling studies indicate that neuronal excitation in L2/3 during sensory response is brought by summation of excitatory postsynaptic potentials (EPSPs) at L4 - L2/3 synapses and recurrent synapses in the L2/3 network (Brecht et al, 2003; Sarid et al, 2007, 2015; de Kock et al, 2007; Lefort et al, 2009) Both of these types of connections involve activation of AMPA and NMDA receptors, which mediate the fast and slow components of EPSPs in L2/3 neurons, respectively (Feldmeyer et al, 2002, 2006; Busetto et al, 2008). The relative contribution of these two types of glutamate receptors to the SEPs and excitation of L2/3 neurons remains incompletely understood

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Discussion

Conclusion