Neuronal Circuits in the Cholinergic Basal Forebrain, Amygdala, and Medial Prefrontal Cortex Contributing to Noxious Stimulus Processing
Barabás Bence
János Szentágothai Neurosciences
Dr. Bereczki Dániel
SE Elméleti Orvostudományi Központ, Beznák Aladár terem
2026-01-12 14:00:00
Functional neurosciences
Dr. Sperlágh Beáta
Dr. Hájos Norbert
Dr. Dávid Csaba
Dr. Tóth Attila
Dr. Csillag András
Dr. Tóth Zsuzsanna
Dr. Rácz Bence
In this thesis, we investigated the cholinergic innervation of the interconnected medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) and examined the impact of noxious stimulation on neuronal spiking in frontal cortical networks. To achieve this, we employed a combination of anatomical tracing, in vivo electrophysiology, and pharmacological interventions.
Using viral tracing techniques, we mapped the projections of cholinergic neurons from two basal forebrain (BF) regions, the horizontal limb of the diagonal band (HDB) and the ventral pallidum/substantia innominata (VP/SI), to the BLA and mPFC. Retrograde and anterograde tracing methods allowed us to determine that these BF areas innervate distinct subregions of the BLA while exhibiting overlapping projections in the mPFC. Additionally, dual-labeling approaches revealed that a subset of cholinergic neurons simultaneously target both the mPFC and BLA, suggesting coordinated neuromodulatory control. Immunohistochemical analyses further demonstrated that VGLUT3 is co-expressed in a significant proportion of VP/SI cholinergic neurons, indicating their potential to release both acetylcholine and glutamate, while cholinergic cells in the HDB and VP/SI do not express VGAT in adult mice.
To investigate the functional impact of cholinergic activation in the frontal cortex, we used in vivo electrophysiology to record neuronal activity following foot shock stimulation. Our recordings showed that HDB and VP/SI cholinergic neurons were strongly activated by noxious stimuli, while cortical pyramidal neurons were diverse in their responses, with some exhibiting excitation while others were inhibited. To dissect the underlying mechanisms, we classified nine interneuron types based on their spiking properties and neurochemical markers, including axo-axonic cells (AACs), parvalbumin-positive basket cells (PVBCs), cholecystokinin-positive basket cells (CCKCB1BCs), vasoactive intestinal polypeptide and cholecystokinin-positive interneurons (VIP/CCK ISIs), VIP/Nkx2.1 ISIs, VIP and choline acetyltransferase (VIP/ChAT ISIs), Neuropeptide-Y-positive neurogliaform (NPY/NGFCs) and somatostatin interneurons (SST INs). Pharmacological manipulations using cholinergic and glutamatergic antagonists confirmed that both neurotransmitter systems contribute to the shock-evoked firing in VIP/CCK ISIs, highlighting the complex interplay between subcortical afferents during aversive experiences.
