Neuroplasticity in Cholinergic Projections from the Basal Forebrain to the Basolateral Nucleus of the Amygdala in the Kainic Acid Model of Temporal Lobe Epilepsy

Abstract

The amygdala is a cerebral region whose function is compromised in temporal lobe epilepsy (TLE). Patients with TLE present cognitive and emotional dysfunctions, of which impairments in recognizing facial expressions have been clearly attributed to amygdala damage. However, damage to the amygdala has been scarcely addressed, with the majority of studies focusing on the hippocampus. The aim of this study was to evaluate epilepsy-related plasticity of cholinergic projections to the basolateral nucleus (BL) of the amygdala. Adult rats received kainic acid (KA) injections and developed status epilepticus. Weeks later, they showed spontaneous recurrent seizures documented by behavioral observations. Changes in cholinergic innervation of the BL were investigated by using an antibody against the vesicular acetylcholine transporter (VAChT). In KA-treated rats, it was found that (i) the BL shrunk to 25% of its original size (p < 0.01 vs. controls, Student’s t-test), (ii) the density of vesicular acetylcholine transporter-immunoreactive (VAChT-IR) varicosities was unchanged, (iii) the volumes of VAChT-IR cell bodies projecting to the BL from the horizontal limb of the diagonal band of Broca, ventral pallidum, and subcommissural part of the substantia innominata were significantly increased (p < 0.05, Bonferroni correction). These results illustrate significant changes in the basal forebrain cholinergic cells projecting to the BL in the presence of spontaneous recurrent seizures.

Cholinergic Signaling, Neural Excitability, and Epilepsy

“…Epilepsy originates from the limbic system, especially from amygdaloid and hippocampal regions. Numerous studies have attempted to explain how the BF cholinergic system projects to the cortex [ 63 ], hippocampus, and amygdala [ 64 , 65 ], which are critical regions for the seizure generation and spread ( Figure 2 ). For example, the changes in the amygdaloidal cholinergic connections from the BF may contribute to epilepsy-related hyperexcitability [ 50 ].…”

The Effect of the APOE-ε4 Allele on the Cholinergic Circuitry for Subjects With Different Levels of Cognitive Impairment

“…Specifically, the Ch4 (i.e., NBM) of the magnocellular cholinergic neurons is the main source of the cholinergic input to the amygdala ( 7 ). The amygdala is a subcortical limbic structure that is densely innervated by cholinergic neurons and is involved in the processing of memory and emotion ( 8 ). Compared with elderly healthy subjects, patients with amnestic mild cognitive impairment (MCI) exhibit a difference in the cholinergic structural correlation, specifically between the atrophy of the NBM and amygdala ( 7 ).…”