Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons.
The neuropeptide galanin colocalizes with choline acetyltransferase, the synthetic enzyme for acetylcholine, in a subset of cholinergic neurons in the basal forebrain of rodents. Chronic intracerebroventricular infusion of nerve growth factor induces a 3- to 4-fold increase in galanin gene expression in these neurons. Here we report the loss of a third of cholinergic neurons in the medial septum and vertical limb diagonal band of the basal forebrain of adult mice carrying a targeted loss-of-function mutation in the galanin gene. These deficits are associated with a 2-fold increase in the number of apoptotic cells in the forebrain at postnatal day seven. This loss is associated with marked age-dependent deficits in stimulated acetylcholine release, performance in the Morris water maze, and induction of long-term potentiation in the CA1 region of the hippocampus. These data provide unexpected evidence that galanin plays a trophic role to regulate the development and function of a subset of septohippocampal cholinergic neurons.
O'Meara
G
G
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, CM20 2QR, United Kingdom.
Coumis
U
U
Ma
S Y
SY
Kehr
J
J
Mahoney
S
S
Bacon
A
A
Allen
S J
SJ
Holmes
F
F
Kahl
U
U
Wang
F H
FH
Kearns
I R
IR
Ove-Ogren
S
S
Dawbarn
D
D
Mufson
E J
EJ
Davies
C
C
Dawson
G
G
Wynick
D
D
D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D019004:Galanin / Q000235:genetics / Q000502:physiology*; D017774:Long-Term Potentiation; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism*
D011950:Receptors, Cholinergic; D019004:Galanin