title: Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: relationship with spatial impairment.
abstract: Both cholinergic and GABAergic projections from the rostral basal forebrain contribute to hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in codistributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase [ChAT] immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 [GAD67] immunopositive) neurons, and total (neuronal nuclei [NeuN] immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline.
authors: Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610-0244, USA.
authors: Cristina
authors: C
authors: Bañuelos
authors: Candi L
authors: CL
authors: LaSarge
authors: Joseph A
authors: JA
authors: McQuail
authors: John J
authors: JJ
authors: Hartman
authors: Ryan J
authors: RJ
authors: Gilbert
authors: Brandi K
authors: BK
authors: Ormerod
authors: Jennifer L
authors: JL
authors: Bizon
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000166:cytology*; D059330:GABAergic Neurons / Q000166:cytology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1