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The Journal of Neuroscience, February 6, 2008, 28(6):1404-1409; doi:10.1523/JNEUROSCI.4851-07.2008

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Brief Communications
Chronic Exposure to Nerve Growth Factor Increases Acetylcholine and Glutamate Release from Cholinergic Neurons of the Rat Medial Septum and Diagonal Band of Broca via Mechanisms Mediated by p75^NTR

Carey Y. L. Huh,¹ Marc Danik,¹ Frédéric Manseau,¹ Louis-Eric Trudeau,² and Sylvain Williams¹

¹Neuroscience Division, Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada H4H 1R3, and ²Department of Pharmacology, Groupe de Recherche sur le Système Nerveux Central, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada H3C 3J7

Correspondence should be addressed to Sylvain Williams, Department of Psychiatry, Douglas Mental Health University Institute, 6875 Lasalle Boulevard, Montréal, Quebec, Canada H4H 1R3. Email: wilsyl{at}douglas.mcgill.ca

Basal forebrain neurons play an important role in memory and attention. In addition to cholinergic and GABAergic neurons, glutamatergic neurons and neurons that can corelease acetylcholine and glutamate have recently been described in the basal forebrain. Although it is well known that nerve growth factor (NGF) promotes synaptic function of cholinergic basal forebrain neurons, how NGF affects the newly identified basal forebrain neurons remains undetermined. Here, we examined the effects of NGF on synaptic transmission of medial septum and diagonal band of Broca (MS-DBB) neurons expressing different neurotransmitter phenotypes. We used MS-DBB neurons from 10- to 13-d-old rats, cultured on astrocytic microislands to promote the development of autaptic connections. Evoked and spontaneous postsynaptic currents were recorded, and neurotransmitters released were characterized pharmacologically. We found that chronic exposure to NGF significantly increased acetylcholine and glutamate release from cholinergic MS-DBB neurons, whereas glutamate and GABA transmission from noncholinergic MS-DBB neurons were not affected by NGF. Interestingly, the NGF-induced increase in neurotransmission was mediated by p75^NTR. These results demonstrate a previously unidentified role of NGF and its receptor p75^NTR; their interactions are crucial for cholinergic and glutamatergic transmission in the septohippocampal pathway.

Key words: corelease; p75^NTR; acetylcholine; glutamate; NGF (nerve growth factor); septum

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Received Oct. 25, 2007; revised Dec. 12, 2007; accepted Dec. 29, 2007.

Correspondence should be addressed to Sylvain Williams, Department of Psychiatry, Douglas Mental Health University Institute, 6875 Lasalle Boulevard, Montréal, Quebec, Canada H4H 1R3. Email: wilsyl{at}douglas.mcgill.ca

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