The nicotinic acetylcholine receptor alpha2 subunit (Chrna2) is a specific marker for oriens lacunosum-moleculare (OLM) interneurons in the dorsal CA1 region of the hippocampus. It was recently shown using a Chrna2-cre mice line that OLM interneurons can modulate entorhinal cortex and CA3 inputs and may therefore have an important role in gating, encoding, and recall of memory. In this study, we have used a combination of electrophysiology and optogenetics using Chrna2-cre mice to determine the role of Chrna2 interneurons in the subiculum area, the main output region of the hippocampus. We aimed to assess the similarities between Chrna2 subiculum and CA1 neurons in terms of the expression of interneuron markers, their membrane properties, and their inhibitory input to pyramidal neurons. We found that subiculum and CA1 dorsal Chrna2 cells similarly expressed the marker somatostatin and had comparable membrane and firing properties. The somas of Chrna2 cells in both regions were found in the deepest layer with axons projecting superficially. However, subiculum Chrna2 cells displayed more extensive projections with dendrites which occupied a significantly larger area than in CA1. The post-synaptic responses elicited by Chrna2 cells in pyramidal cells of both regions revealed comparable inhibitory responses elicited by GABAA receptors and, interestingly, GABAB receptor mediated components. This study provides the first in-depth characterization of Chrna2 cells in the subiculum, and suggests that subiculum and CA1 Chrna2 cells are generally similar and may play comparable roles in both sub-regions.

The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3 weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5 weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing.

Circuit interactions within the medial entorhinal cortex (MEC) translate movement into a coherent code for spatial location. Entorhinal principal cells are subject to strong lateral inhibition, suggesting that a disinhibitory mechanism may drive their activation. Cortical Vasoactive Intestinal Peptide (VIP) expressing inhibitory neurons are known to contact other interneurons and excitatory cells and are thus capable of providing a local disinhibitory mechanism, yet little is known about this cell type in the MEC. To investigate the electrophysiological and morphological properties of VIP cells in the MEC, we use in vitro whole-cell patch-clamp recordings in VIPcre/tdTom mice. We report several gradients in electrophysiological properties of VIP cells that differ across laminae and along the dorsal-ventral MEC axis. We additionally show that VIP cells have distinct morphological features across laminae. Together, these results characterize the cellular and morphological properties of VIP cells in the MEC.