PhD Scientific Days 2022

Neurosciences II.

Immunhistochemical characterization of the human and mouse septal area

Text of the abstract

Associative learning is essential in adaptation to our continuously changing environment. It is well established that basal forebrain (BF) nuclei play an important role in learning mechanisms. Although malfunction of basal forebrain cholinergic neurons (BFCNs) is closely linked to the patomechanism of Alzheimer’s dementia, very little is known about other forebrain cholinergic cell populations.
Lateral to the medial septal nucleus lies the lateral septum (LS), which previously have been identified as a mainly GABAergic nucleus. Our colleagues – in coherence with early anatomical studies – identified a significant cholinergic neuronal population in the LS. The area presumably plays an important role in social learning and pathological function of this area is associated with anxiety, mood disorders and schizophrenia. Moreover, dementia and age-related neuronal changes affect this area as well.
We hypothetize that cholinergic neurons of the LS play a major role in associative learning as well as BF neuronal populations, therefore we would like to study the neurochemical composition and cellular anatomy of this area more extensively. In our experiments we are examining the coexpression patterns and morphology of lateral septal cholinegic neurons with light- and electron microscopic techniques. We extrapolate our findings by replicating our experiments on human septal complex tissue samples.
Our preliminary findings indicate that a major population of LS cholinergic neurons show calbindin-positivity (CB+) as well. By using 3xTg transgenic Alzheimer’s disease model mouse line, we show that LS is also affected by ß-amiloid plaque formation. These plaques are surrounding CB+ (putative cholinergic) neurons. We managed to show an extensive CB+ neuronal populations in the human septal complex as well. In the future, we would like to confirm the possible coexpression of CB and cholinergic neuronal marker ChAT (cholin-acetyltransferase) in the human LS and characterize the possible morphological changes of cholinergic neurons associated with dementia.

This work was supported by the European Research Council Starting Grant no. 715043 to B.H.; the New National Excellence Program of the Ministry of Innovation and Technology (ÚNKP-21-3-II) to P.H and the National Brain Research Program (2017-1.2.1-NKP-2017-00002) to ZS.M.