The role of basal forebrain cholinergic and gabaergic neurons in pavlovian conditioning
Jámbor-Hegedüs Panna
János Szentágothai Neurosciences
Dr. Bereczki Dániel
SE Patológiai, Igazságügyi és Biztosítási Orvostani Intézet
2024-04-04 15:30:00
Functional neurosciences
Dr. Sperlágh Beáta
Dr. Hangya Balázs
Dr. Dobolyi Árpád
Dr. Tóth Kinga
Dr. Csillag András
Dr. Zachar Gergely
Dr. Varró Petra
BF consists of subcortical nuclei characterized by the presence of cholinergic neurons (BFCNs). BFCNs represent 5-10% of the neurons in the BF. Besides BFCNs, glutamatergic and multiple subtypes of GABAergic neurons are found in the basal forebrain. The degeneration of BFCNs have been found in brain tissue samples of patients with Alzheimer’s disease, indicating a relationship between BFCN function, memory and learning (cognitive processes that are severely affected by the disease).
By studying the role of the BF (and BFCNs) in animal experimental models, a causal role between BF neuronal activity and learning, memory and attention have been established. Moreover, it was found that not only BFCNs, but non-cholinergic BF neurons are also involved in cognitive processes.
During my PhD studies, we examined the function of BFCNs, BFPVNs and VP neurons in Pavlovian conditioning – a simple reinforcement learning task. We found that BFCNs not only respond to conditioned and unconditioned stimuli with short latency, phasic activation, but they showed stronger activation to reward predicting cues and surprising rewards.
When we recorded BFPVN activity, we noticed that they responded with phasic activation to punishment in Pavlovian conditioning. However, BFPVN optogenetic activation did not elicit aversion, meanwhile optogenetic silencing of BFPVNs disrupted learning of task contingencies. By using antero- and retrograde tracing methods, we revealed that BFPVNs establish extensive projections to the medial septum, hippocampus, retrosplenial cortex, limbic and frontal areas and receive inputs conveying nociceptive information.
VP neurons responded to positive and negative reinforcement, as well as predictive cues during Pavlovian conditioning. Moreover, non-bursting, non-rhythmic VP neurons, forming synchronously activated assemblies, responded more to salient events. A subset of VP neurons exhibited differential burst and single spikes response to behaviorally relevant events.
In conclusion, BF nuclei are key areas conveying important information for learning; however, each BF nucleus (and even cell types) are representing different aspects of such events. We hope, our work shed light on how BF nuclei contribute to memory and learning processes.
