Sources of spatial tuning in the dorsal subiculum

Spatial navigation is an essential behavior for all moving life-forms. A main mammalian brain structure implicated in this process is the hippocampal formation. Neuronal firing patterns in this brain region are remarkably correlated to various aspects of the animal’s location and navigation. The subiculum is a primary output structure of hippocampal information processing, providing output to various cortical and subcortical areas. With this crucial position within the hippocampal formation, the primary role of the subiculum is to integrate, compress and then distribute hippocampally-processed information to the whole brain. Two major inputs to the subiculum arise from the CA1 region and the entorhinal cortex. This study investigates the individual roles of these two input streams in generating spatially correlated firing of subicular neurons. In vivo whole cell patch clamp recordings in mice running freely on a circular track revealed that dorsal subicular neurons receive spatially tuned input. Additionally, channelrodopsin assisted circuit mapping showed, that the two major input streams target specific regions in the dendritic tree of dorsal subicular neurons. Specifically, CA1 input is located more proximal, while EC input forms synapses in the distal part of the dendritic tree of dorsal subicular neurons. Finally, individual contributions of both input streams on the spatial tuning of dorsal subicular neurons were investigated using two-photon calcium imaging in mice running on a linear treadmill. Chemogenetic inactivation of either CA1 or entorhinal cortex inputs via viral transduction of the inhibitory DREADD and local application of CNO by a small hole in the imaging window, revealed district contributions of both inputs paths: CA1 inputs are necessary for the place and velocity tuning, while EC inputs are only necessary for the place tuning of dorsal subicular neurons. Taken together my experiments demonstrate that (I) subicular neurons receive spatial and velocity tuned input (II), that subicular neurons maintain a functional input segregation between CA1 and entorhinal cortex synapses and (III) that both input streams play differential roles in shaping the spatial tunings of subicular neurons with respect to place and movement speed. This study emphasizes the need to differentiate between the information that one brain region could potentially receive from other brain regions and the information that is actually used by the postsynaptic neuron during their input-output transformation

obarnstedt/septum-vta: v1.0.0

<p>Release accompanying proof submission for Mocellin et al. (2024)</p&gt

Electrophysiological profiles of cell-types in medial entorhinal cortex

This dataset shows electrophysiological profiles of different whole-cell patch-clamp recorded cell-types in the medial entorhinal cortex that receive monosynaptic input form the medial septum and diagonal band of broca.<div><br></div><div>DataSheets.pdf contains an overview of the electrophysiolgical characteristica, the .txt files contain raw data traces measured in mV. The first line contains headers, the first column is time. The tab-delimited columns refer to current injections of -200, -100, -50, -30, -20, -10, 10, 20, 30, 50, 100, 200, 300, 400, 500 pA. The data are sampled at 100 kHz. </div><div><br></div><div>For details refer to the original publication.</div

Loss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability

Dendritic spines are postsynaptic domains that shape structural and functional properties of neurons. Upon neuronal activity, Ca2+ transients trigger signaling cascades that determine the plastic remodeling of dendritic spines, which modulate learning and memory. Here, we study in mice the role of the intracellular Ca2+ channel Ryanodine Receptor 2 (RyR2) in synaptic plasticity and memory formation. We demonstrate that loss of RyR2 in pyramidal neurons of the hippocampus impairs maintenance and activity-evoked structural plasticity of dendritic spines during memory acquisition. Furthermore, post-developmental deletion of RyR2 causes loss of excitatory synapses, dendritic sparsification, overcompensatory excitability, network hyperactivity and disruption of spatially tuned place cells. Altogether, our data underpin RyR2 as a link between spine remodeling, circuitry dysfunction and memory acquisition, which closely resemble pathological mechanisms observed in neurodegenerative disorders

A septal-ventral tegmental area circuit drives exploratory behavior

To survive, animals need to balance their exploratory drive with their need for safety. Subcortical circuits play an important role in initiating and modulating movement based on external demands and the internal state of the animal; however, how motivation and onset of locomotion are regulated remain largely unresolved. Here, we show that a glutamatergic pathway from the medial septum and diagonal band of Broca (MSDB) to the ventral tegmental area (VTA) controls exploratory locomotor behavior in mice. Using a self-supervised machine learning approach, we found an overrepresentation of exploratory actions, such as sniffing, whisking, and rearing, when this projection is optogenetically activated. Mechanistically, this role relies on glutamatergic MSDB projections that monosynaptically target a subset of both glutamatergic and dopaminergic VTA neurons. Taken together, we identified a glutamatergic basal forebrain to midbrain circuit that initiates locomotor activity and contributes to the expression of exploration-associated behavior