TY  - JOUR
AU  - Mocellin, Petra
AU  - Barnstedt, Oliver
AU  - Luxem, Kevin
AU  - Kaneko, Hiroshi
AU  - Vieweg, Silvia
AU  - Henschke, Julia
AU  - Dalügge, Dennis
AU  - Fuhrmann, Falko
AU  - Karpova, Anna
AU  - Pakan, Janelle M P
AU  - Kreutz, Michael R
AU  - Mikulovic, Sanja
AU  - Remy, Stefan
TI  - A septal-ventral tegmental area circuit drives exploratory behavior.
JO  - Neuron
VL  - 112
IS  - 6
SN  - 0896-6273
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2024-00307
SP  - 1020 - 1032.e7
PY  - 2024
AB  - 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.
KW  - Mice
KW  - Animals
KW  - Ventral Tegmental Area: physiology
KW  - Exploratory Behavior
KW  - Dopaminergic Neurons: metabolism
KW  - Motivation
KW  - VTA (Other)
KW  - behavioral quantification (Other)
KW  - exploration (Other)
KW  - glutamatergic neurons (Other)
KW  - locomotion (Other)
KW  - medial septum (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38266645
DO  - DOI:10.1016/j.neuron.2023.12.016
UR  - https://pub.dzne.de/record/268731
ER  -