PhD Scientific Days 2024

Poster Session D - Neurosciences 1.

Anatomical, electrophysiological and functional characterization of lateral septal cholinergic neurons.

Text of the abstract

Introduction:
The lateral septum (LS) integrates a plethora of subcortical and cortical inputs to generate appropriate affective behavioral responses related to memory, reward, social behaviors, and fear. Contrary to the medial septum, the LS is considered an entirely GABAergic nucleus where neurons express diverse GABAergic markers.
Aims: We aimed to examine the cellular composition of the lateral septum, with special emphasis on the alleged presence of cholinergic neurons. Methods: To answer these questions, we use a combination of genetic, anatomical, electrophysiological, behavioral, and imaging tools.
Results: Here we describe a neglected and underappreciated neuronal subclass in the LS expressing choline-acetyltransferase (ChAT) an enzyme responsible for the synthesis of the neurotransmitter acetylcholine, therefore named Lateral Septum Cholinergic Neurons (LSCNs).
ChAT expressing neurons are immunohistochemically detectable in mouse, macaque, and post-mortem human LS sections, discontinuous of MS cholinergic cells. Furthermore, LSCNs can be selectively targeted in multiple independent transgenic mouse lines. Using AAV-mediated anterograde, and ΔRabies mediated retrograde tracings, we reveal that LSCNs integrate inputs from the hippocampus, hypothalamic areas, and the basal forebrain, furthermore project robustly to the hypothalamus and the medial amygdala. In vitro, electrophysiological recordings of hypothalamic neurons show acetylcholine release from LSCN axons. To better understand their function, we parallelly recorded LSCN activity (GCaMP8) and their ACh release (ACh3.0) during a head-restrained probabilistic Pavlovian conditioning task and freely moving behaviors via fiber photometry. Optical recordings revealed that LSCNs are activated by different types of aversive stimuli (air puff, foot shock), but respond robustly to reward and social stimuli as well, and responses are paralleled by ACh release in LSCN target regions.
Conclusions: Our results strongly support that the LS is not a homogenous GABAergic nucleus, but contains an evolutionary conserved cholinergic cell population.
Funding: D.S is supported by ÚNKP-23-4-II New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund. This work is supported by NKFIH KH125294, NKFIH K135561 and the NAP 3.0.