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  • Optogenetic activation of cajal-retzius cells reveals their glutamatergic output and a novel feedforward circuit in the developing mouse hippocampus.

Optogenetic activation of cajal-retzius cells reveals their glutamatergic output and a novel feedforward circuit in the developing mouse hippocampus.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2014-09-26)
Giulia Quattrocolo, Gianmaria Maccaferri
ABSTRACT

Cajal-Retzius cells orchestrate the development of cortical circuits by secreting the glycoprotein reelin. However, their computational functions are still unknown. In fact, the nature of their postsynaptic targets, major neurotransmitter released, as well as the class of postsynaptic receptors activated by their firing remain unclear. Here, we have addressed these questions by activating Cajal-Retzius cells optogenetically in mouse hippocampal slices. Light delivered to stratum lacunosum-moleculare triggered EPSCs both on local interneurons and on pyramidal cells. Responses recorded under voltage-clamp conditions had identical short latencies and similar amplitudes, but were kinetically different (i.e., faster in interneurons vs pyramidal cells). In both cases, responses were blocked by TTX, indicating that they were generated by action potential-dependent release. Responses in interneurons were rescued by the addition of 4-AP to TTX, and decreased when presynaptic firing in Cajal-Retzius cells was reduced by the chemokine CXCL12, indicating the existence of a direct Cajal-Retzius cell-interneuron monosynaptic connection. Although the combined application of 4-AP and TTX did not rescue responses in pyramidal cells, neither were they affected by the GABAA receptor blocker gabazine, which would be expected if they were polysynaptic. Both connections showed physiological and pharmacological properties indicating the involvement of AMPA- and NMDA-type glutamate receptors. The connectivity from presynaptic Cajal-Retzius cells to interneurons was strong enough to generate long-latency feedforward GABAergic input onto pyramidal cells. We propose that this newly defined Cajal-Retzius cell-dependent microcircuit may regulate synaptic plasticity and dendritic development in stratum lacunosum-moleculare, thus impacting the integrative properties of the developing hippocampus.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Osmium tetroxide solution, suitable for electron microscopy, 2% in H2O
Sigma-Aldrich
Osmium tetroxide, Sealed ampule.
Sigma-Aldrich
Osmium tetroxide solution, suitable for electron microscopy, 4% in H2O
Sigma-Aldrich
Osmium tetroxide, ReagentPlus®, 99.8%
Sigma-Aldrich
Osmium tetroxide solution, 4 wt. % in H2O
Sigma-Aldrich
Osmium tetroxide solution, 2.5 wt. % in tert-butanol
Sigma-Aldrich
Osmium tetroxide, ACS reagent, ≥98.0%
Sigma-Aldrich
Anti-Reelin Antibody, a.a. 164-496 mreelin, clone G10, clone G10, Chemicon®, from mouse
Sigma-Aldrich
Os EnCat® 40, extent of labeling: 0.3 mmol/g Os loading