Effect of basal forebrain stimulation on regional blood flow and extracellular acetylcholine release in the piriform cortex.

Abstract

Introduction: The piriform cortex receives substantial cholinergic innervation from neurons in the horizontal limb of the diagonal band of Broca (HDB) within the basal forebrain. This study investigated whether chemical stimulation of the HDB increases regional blood flow and extracellular acetylcholine (ACh) levels in the piriform cortex and whether the evoked hemodynamic response depends on cholinergic receptor activation.

Methods: The experiments were performed on 15 adult male Fischer 344 rats. Under anesthesia, regional blood flow in the piriform cortex was measured using laser Doppler flowmetry. Extracellular ACh concentrations there were determined using microdialysis coupled with high-performance liquid chromatography and electrochemical detection (HPLC-ECD). Focal chemical stimulation of unilateral HDB was performed by microinjection of L-glutamate (50-100 nmol).

Results: Following HDB stimulation with L-glutamate at doses of 50 and 100 nmol, regional blood flow in the ipsilateral piriform cortex increased to approximately 112% and 127% of prestimulus baseline levels, respectively. Mean arterial pressure was not significantly affected by HDB stimulation. In rats pretreated intravenously with the cholinergic receptor antagonists atropine and mecamylamine, HDB stimulation did not alter blood flow in the piriform cortex. HDB stimulation also increased extracellular ACh concentrations in the ipsilateral piriform cortex.

Conclusion: This study showed that stimulation of HDB neurons in the basal forebrain increases regional blood flow in the piriform cortex, accompanied by an increase in ACh release in the same region, and that cholinergic receptor blockade abolishes this blood flow response. Impaired cholinergic input in this region may disrupt hemodynamic regulation, leading to olfactory dysfunction.