Whisker experience modulates long‐term depression in neocortical γ‐aminobutyric acidergic interneurons in barrel cortex

Abstract

Long-term plasticity is believed to be an important mechanism that allows neural circuits to be modulated in an use-dependent manner. However, evidence regarding the role of sensory experience in modulating long-term plasticity of glutamatergic synapses in neocortical GABAergic interneurons is unavailable. Here, we focused on regular-spiking nonpyramidal (RSNP) interneurons and examined spike-pairing-induced plasticity of glutamatergic synapses and its modulation by sensory experiences ex vivo. In our previous studies, RSNP interneurons do not show experience-dependent plasticity of intrinsic properties or alteration of thalamocortical (TC) synapses and exhibit robust modulation by mGluRs. Here we report a spike-pairing-induced long-term depression (spLTD) of glutamatergic synapses in RSNP interneurons of barrels cortex. Using paired recording and thalamic-induced responses, we found that the spLTD was specific for intracortical but not TC synapses. The spLTD was mediated via presynaptic mGluRs. The spLTD was not modulated by chronic or acute administration of NMDAR antagonists but was enhanced by sensory deprivation (via whisker trimming) during a postnatal sensitive period ex vivo. The synapses specific spLTD to intracortical glutamatergic synapses in RSNP cells and their modulation by sensory deprivation may contribute to sensory-dependent remodeling of cortical circuits and redistribution circuit activity along the whisker-related columns.

Plasticity of Inhibition

“…In FS interneurons of the somatosensory cortex, in contrast, one study reported mGluR-dependent LTD whether the presynaptic spike preceded or followed the postsynaptic spike (Lu et al, 2007). A similar pattern was observed at intracortical glutamatergic synapses on regular-spiking interneurons in barrel cortex (Sun and Zhang, 2011). mGluR5 receptors also play a central role in NMDA-independent LTP of excitatory postsynaptic potentials in FS interneurons of the visual cortex (Sarihi et al, 2008).…”

“…Although equivalent data are not available in the somatosensory cortex, whisker trimming has been shown to facilitate LTD of glutamatergic synapses elicited by an STDP protocol in regular-spiking interneurons (Sun and Zhang, 2011). Recent in vivo imaging has also revealed extensive structural plasticity of GABAergic synapses affected by whisker trimming van Versendaal et al, 2012).…”

Circuit Mechanisms Underlying Epileptogenesis in a Mouse Model of Focal Cortical Malformation

“…53,54 In canonical cortical circuitry, L2/3 receives its prominent excitatory drive from L4 and subsequently sends a major output to L5B. 40 In a healthy barrel cortex, L2/3 PCs display a lower synaptic E/I ratio compared to L5B PCs within the same columns, 29,51,55 consistent with their respective functions, e.g., the sparse coding strategy used by supragranular neurons for feature integration 56,57 and active feedback to subcortical regions. 34,58 L2/3 PCs also send their outputs to other ipsi-and contra-lateral cortical regions.…”

“…It has been well documented that synaptic excitation and inhibition in cortical neurons show a proportionality, or balance, through the use of recurrent local synaptic connections to maintain normal brain functions. 29,37,[47][48][49][50][51][52] L2/3 and L5B PCs play different roles in the horizontal propagation of recurrent-network activities, including epileptiform activities. 53,54 In canonical cortical circuitry, L2/3 receives its prominent excitatory drive from L4 and subsequently sends a major output to L5B.…”