Modulation of prefrontal cortex function by basal forebrain cholinergic and GABAergic neurons at the behavioral and molecular level

Abstract

The present research aimed to study the effects of selective immunolesions of cholinergic or gamma-aminobutyric acid (GABA)ergic neurons in the nucleus basalis magnocellularis (NBM) on memory function as well as cholinergic activity and the level of expression of glutamatergic [NR2B subunit of N-methyl-D-aspartate(NMDA)] receptors in the medial prefrontal cortex (mPFC) and hippocampus of behaviorally characterized rats. In behavioral experiments, working memory was assessed by a spatial alternation testing procedure in a plus-maze, and acquisition and retention of spatial memory was evaluated in a Morris water maze. The rats were divided into three groups: the NBM cholinergic, GABAergic immunolesioned groups and the normal control group. Cholin acetyltransferase or parvalbumin staining of the NBM and acetylcholinesterase staining of the mPFC and hippocampal sections were performed to visualize the effects of immunotoxins. The electrophoresis and immunoblotting were run to evaluate the effect of NBM lesions on the amount of the NR2B subunit of NMDA receptors. The results indicate that the immunolesion of cholinergic NBM neurons impair spatial working memory, as well as long-term spatial memory which is accompanied by significant changes in glutamatergic (the NR2B subunit of NMDA receptor) and cholinergic markers in the mPFC, whereas immunolesion of GABAergic NBM neurons does not affect long-term spatial memory, it does though cause the impairment of working memory with a reduction of the NMDA NR2B receptor signaling in the mPFC. The present results demonstrate that the cholinergic and GABAergic NBM cell groups play diverse and complementary roles and are integrated in distinct NBM-mPFC networks that may play different roles in mPFC memory function.

The role of the basal forebrain in general anesthesia

“…Large‐diameter neurons were more centralized in the SI, HDB, and MCPO. Medium‐diameter neurons were the highest in the HDB and the MCPO, whereas small‐diameter neurons were more centralized in the VP 17 …”

“…Mediumdiameter neurons were the highest in the HDB and the MCPO, whereas small-diameter neurons were more centralized in the VP. 17 In 2015, using an electrophysiological method, Jones found a relationship between the discharge patterns of GABA neurons and urethane anesthesia. There are two types of discharge patterns of GABA neurons under urethane anesthesia.…”

“…For instance, whole‐brain imaging reveals that the synaptic terminals of BF cholinergic neurons project to the hippocampus, the prefrontal cortex (PFC), the periaqueductal gray (PAG), the lateral habenula (LHb), and the lateral hypothalamus (LH) 14,15 . GABA neurons in BF project to the ventral tegmental area (VTA), 16 PFC, the substantia negra (SNc), the retrorubral field (RRF), the parabrachial (PB), the locus coeruleus (LC), the laterodorsal tegmental nucleus (LDT), the dorsal raphe nucleus (DRN), and PAG 17 . Glutamatergic neurons in BF mainly project to VTA, RRF, DRN, LDT, LHb, LDT, and PFC 18 .…”

“… 14 , 15 GABA neurons in BF project to the ventral tegmental area (VTA), 16 PFC, the substantia negra (SNc), the retrorubral field (RRF), the parabrachial (PB), the locus coeruleus (LC), the laterodorsal tegmental nucleus (LDT), the dorsal raphe nucleus (DRN), and PAG. 17 Glutamatergic neurons in BF mainly project to VTA, RRF, DRN, LDT, LHb, LDT, and PFC. 18 BF receives dense inputs from diverse brain regions.…”

“…Medium‐diameter neurons were the highest in the HDB and the MCPO, whereas small‐diameter neurons were more centralized in the VP. 17 …”