mGlu1α-dependent recruitment of excitatory GABAergic input to neocortical Cajal-Retzius cells

Cajal-Retzius cells are thought to play an important role for cortical development, and receive primarily spontaneous GABAergic input mediated by GABAA receptors. However, neither the effects of synaptically-released GABA on their excitability nor the cellular source(s) of spontaneous GABAergic currents have been yet determined. By directly recording electrophysiological responses from identified Cajal-Retzius cells of the CXCR4-EGFP mouse, we show that GABAergic input can trigger supra-threshold responses, and that the pharmacological activation of mGlu1α receptors with the group I agonist DHPG powerfully increases the frequency of spontaneous GABAergic currents. These effects appeared mediated by a network mechanism, because responses to DHPG were completely prevented both by surgical disconnection of layer I from lower layers and by exposure of slices to TTX.We propose that the cellular source underlying the observed effect of DHPG are layer I-targeting Martinotti-like interneurons, which we show express functional group I mGluRs and respond to DHPG with supra-threshold depolarization already at early developmental stages.In conclusion, our work suggests that conditions of enhanced glutamate release may be critical at early developmental stages for the recruitment of an mGlu1α-dependent micro-circuit, which then leads to the activation of Cajal-Retzius cells.

► Spontaneous synaptic currents in Cajal-Retzius cells (CRs) are GABAergic.
► The frequency of these currents is massively increased by mGlu1α activation.
► This effect requires firing in cortical layers below layer I.
► DHPG triggers firing in layer II/III Martinotti interneurons (Ms).
► Ms of layer II/III are proposed to be a critical source of synaptic input to CRs.