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This Article Full Text Full Text (PDF) All Versions of this Article: 102/4/2194    most recent 00301.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Murchison, D. Articles by Griffith, W. H. PubMed PubMed Citation Articles by Murchison, D. Articles by Griffith, W. H.

RESEARCH-ARTICLE

Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

¹Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center; and ²Department of Psychology, Texas A&M University, College Station, Texas

Submitted 6 June 2009; accepted in final form 5 August 2009

ABSTRACT

Alterations in neuronal Ca²⁺ homeostasis are important determinants of age-related cognitive impairment. We examined the Ca²⁺ influx, buffering, and electrophysiology of basal forebrain neurons in adult, middle-aged, and aged male F344 behaviorally assessed rats. Middle-aged and aged rats were characterized as cognitively impaired or unimpaired by water maze performance relative to young cohorts. Patch-clamp experiments were conducted on neurons acutely dissociated from medial septum/nucleus of the diagonal band with post hoc identification of phenotypic marker mRNA using single-cell RT-PCR. We measured whole cell calcium and barium currents and dissected these currents using pharmacological agents. We combined Ca²⁺ current recording with Ca²⁺-sensitive ratiometric microfluorimetry to measure Ca²⁺ buffering. Additionally, we sought changes in neuronal firing properties using current-clamp recording. There were no age- or cognition-related changes in the amplitudes or fractional compositions of the whole cell Ca²⁺ channel currents. However, Ca²⁺ buffering was significantly enhanced in cholinergic neurons from aged cognitively impaired rats. Moreover, increased Ca²⁺ buffering was present in middle-aged rats that were not cognitively impaired. Firing properties were largely unchanged with age or cognitive status, except for an increase in the slow afterhyperpolarization in aged cholinergic neurons, independent of cognitive status. Furthermore, acutely dissociated basal forebrain neurons in which choline acetyltransferase mRNA was detected had the electrophysiological profiles of identified cholinergic neurons. We conclude that enhanced Ca²⁺ buffering by cholinergic basal forebrain neurons may be important during aging.