Neuron: Youming Lu/Lingqiang Zhu's team at Huazhong University of Science and Technology reveals two types of cholinergic neurons that regulate anxiety and spatial memory

Cholinergic neurons in the medial septal (MS) are the main source of cholinergic input to the forebrain and regulate multiple functions
such as sensory processing, memory, and attention.

Cholineacetyltransferase (ChAT) is an enzyme that synthesizes acetylcholine neurotransmitters and is widely used to label cholinergic neurons
.

D28K is a calcium-ion-binding protein whose expression is thought to have a protective effect
on calcium-ion-dependent neuronal degeneration.

On September 20, 2022, the research team of Lu Youming/Zhu Lingqiang of Tongji Medical College of Huazhong University of Science and Technology published an article in the journal Neuron that revealed that there are two types of cholinergic neurons with different structures (projected to different hippocampal regions) and different functions (anxiety behavior and spatial memory) in the medial septal nucleus
.

1

Two classes of cholinergic neurons with different anatomical structures

Fluorescence in situ hybridization found that MS-region ChAT labeled neurons all expressed inhibitory neuron markers, and some neurons expressed D28K and did not express excitatory neuron markers
.

There are differences between the two types of neurons in terms of electrophysiological function: D28K positive neurons show bipolar morphology and action potential has low discharge frequency, while D28K negative neurons show multipolar morphology and action potential shows high discharge frequency
.

Viral tracing experiments have found that MS-region D28K-positive neurons and D28K-negative neurons project to multiple brain regions of the whole brain, of which the main brain regions are cortical and hippocampal regions
.

Figure 1: Spatial distribution of D28K-positive neurons in the medial septal nucleus

2

Two different classes of molecules define cholinergic neurons

Single-cell sequencing technology found that D28K-positive neurons enriched and expressed kcnh1 gene (encoding Eag1 potassium channel) in large quantities, and D28K negative neurons enriched expressing cacna1h gene (encoding low-voltage gated calcium channels).

Figure 2: Single-cell sequencing reveals molecular signatures of different cholinergic neurons

3

Two classes of cholinergic neurons with different functions

Specific knockout mouse MS region D28K positive neuron kcnh1 gene does not affect spatial memory function, the number and time of entry into the open arm in overhead experiments are reduced, showing anxiety phenotype, and injection of cholinergic receptor antagonists in the ventral hippocampus CA1 region can block the occurrence
of this anxiety behavior.

Cholinergic neuronal activity in the basal forebrain influences changes in excitatory synaptic transmission and induces hippocampal thetatic oscillatory activity
.

Figure 3: Two different classes of cholinergic neurons regulate different behaviors

summary

This paper found that there are two different types of cholinergic neurons in the medial septal nucleus: D28K-positive neurons, which regulate anxiety behavior, and D28K-negative neurons, which regulate spatial memory function
.

Original Source:

Li et al.