Behavioural Brain Research 195 (2008) 86–97
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Behavioural Brain Research
journal homepage: www.elsevier.com/locate/bbr
Review
Modulation of cholinergic functions by serotonin and possible implications in
memory: General data and focus on 5-HT
1A
receptors of the medial septum
H
´
el
`
ene Jeltsch-David
∗
, Julie Koenig, Jean-Christophe Cassel
Laboratoire d’Imagerie et de Neurosciences Cognitives, UMR 7191, Universit
´
e Louis Pasteur/CNRS, IFR 27 des Neurosciences et GDR 2905 du CNRS,
12 rue Goethe, F-67000 Strasbourg, France
article info
Article history:
Received 1 December 2007
Received in revised form 22 February 2008
Accepted 22 February 2008
Available online 4 March 2008
Keywords:
5-HT
5-HT
1A
receptor
192 IgG-saporin
Acetylcholine
Cognition
GABA
Hippocampus
Septum
abstract
Cholinergic systems were linked to cognitive processes like attention and memory. Other neurotrans-
mitter systems having minor influence on cognitive functions – as shown by the weakness of the
effects of their selective lesions – modulate cholinergic functions. The serotonergic system is such a
system. Conjoined functional changes in cholinergic and serotonergic systems may have marked cog-
nitive consequences [Cassel JC, Jeltsch H. Serotoninergic modulation of cholinergic function in the central
nervous system: cognitive implications. Neuroscience 1995;69(1):1–41; Steckler T, Sahgal A. The role
of serotoninergic–cholinergic interactions in the mediation of cognitive behaviour. Behav Brain Res
1995;67:165–99].
A crucial issue in that concern is the identification of the neuroanatomical and neuropharmacolog-
ical substrates where functional effects of serotonergic/cholinergic interactions originate. Approaches
relying on lesions and intracerebral cell grafting, on systemic drug-cocktail injections, or even on
intracerebral drug infusions represent the main avenues on which our knowledge about the role of
serotonergic/cholinergic interactions has progressed.
The present review will visit some of these avenues and discuss their contribution to what is currently
known on the potential or established implication(s) into memory functions of serotonergic/cholinergic
interactions. It will then focus on a brain region and a neuropharmacological substrate that have been
poorly studied as regards serotonergic modulation of memory functions, namely the medial septum and
its 5-HT
1A
receptors. Based on recent findings of our laboratory, we suggest that these receptors, located
on both cholinergic and GABAergic septal neurons, take part in a mechanism that controls encoding, to
some extent consolidation, but not retrieval, of hippocampal-dependent memories. This control, however,
does not occur by the way of an exclusive action of serotonin on cholinergic neurons.
© 2008 Elsevier B.V. All rights reserved.
Contents
1. Introduction .......................................................................................................................................... 87
2. Lesion and cell grafting approaches.................................................................................................................. 87
2.1. Serotonergic and cholinergic neurotoxins .................................................................................................... 87
2.2. Combined cholinergic and serotonergic lesions .............................................................................................. 88
2.3. Co-grafting fetal cell suspensions rich in cholinergic and serotonergic neurons ............................................................ 89
3. Systemic drug administration combined to other approaches ...................................................................................... 89
3.1. Modulation of cholinergic graft-induced effects by systemic treatment with serotonergic drugs .......................................... 89
3.2. Effects of serotonergic drugs after cholinergic lesions or receptor blockade ................................................................ 90
4. Intracerebral drug infusion approaches: focus on 5-HT
1A
receptors of the medial septum ........................................................ 90
4.1. Acquisition of a reference-memory task in the water maze under activation of septal 5-HT
1A
receptors................................... 91
4.2. Spatial working-memory in a water-maze and septal 5-HT
1A
receptors.................................................................... 91
4.3. Are 5-HT
1A
receptors of the medial septum a target of serotonin-mediated mechanisms underlying encoding and consolidation
processes? ...................................................................................................................................... 92
∗
Corresponding author. Tel.: +33 390 24 19 31; fax: +33 390 24 19 58.
E-mail address: helene.david@linc.u-strasbg.fr (H. Jeltsch-David).
0166-4328/$ – see front matter © 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.bbr.2008.02.037