title: Characterization of age-related changes in synaptic transmission onto F344 rat basal forebrain cholinergic neurons using a reduced synaptic preparation.
abstract: Basal forebrain (BF) cholinergic neurons participate in a number of cognitive processes that become impaired during aging. We previously found that age-related enhancement of Ca(2+) buffering in rat cholinergic BF neurons was associated with impaired performance in the water maze spatial learning task (Murchison D, McDermott AN, Lasarge CL, Peebles KA, Bizon JL, and Griffith WH. J Neurophysiol 102: 2194-2207, 2009). One way that altered Ca(2+) buffering could contribute to cognitive impairment involves synaptic function. In this report we show that synaptic transmission in the BF is altered with age and cognitive status. We have examined the properties of spontaneous postsynaptic currents (sPSCs) in cholinergic BF neurons that have been mechanically dissociated without enzymes from behaviorally characterized F344 rats. These isolated neurons retain functional presynaptic terminals on their somata and proximal dendrites. Using whole cell patch-clamp recording, we show that sPSCs and miniature PSCs are predominately GABAergic (bicuculline sensitive) and in all ways closely resemble PSCs recorded in a BF in vitro slice preparation. Adult (4-7 mo) and aged (22-24 mo) male rats were cognitively assessed using the water maze. Neuronal phenotype was identified post hoc using single-cell RT-PCR. The frequency of sPSCs was reduced during aging, and this was most pronounced in cognitively impaired subjects. This is the same population that demonstrated increased intracellular Ca(2+) buffering. We also show that increasing Ca(2+) buffering in the synaptic terminals of young BF neurons can mimic the reduced frequency of sPSCs observed in aged BF neurons.
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, Bryan, Texas; and.
authors.forename: William H
authors.initials: WH
authors.lastname: Griffith
authors.forename: Dustin W
authors.initials: DW
authors.lastname: Dubois
authors.forename: Annette
authors.initials: A
authors.lastname: Fincher
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Peebles
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bizon
authors.forename: David
authors.initials: D
authors.lastname: Murchison
mesh_terms: D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000378:metabolism; D059329:Cholinergic Neurons / Q000378:metabolism / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D055369:Miniature Postsynaptic Potentials; D016548:Prosencephalon / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid; D002118:Calcium
keywords: GABA; aging; basal forebrain; behavior; synaptic transmission