Partial loss in septo-hippocampal cholinergic neurons alters memory-dependent measures of brain connectivity without overt memory deficits.
Neurobiology of Disease. 2013-06-01; 54: 372-381
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1. Neurobiol Dis. 2013 Jun;54:372-81. doi: 10.1016/j.nbd.2013.01.010. Epub 2013 Jan
Partial loss in septo-hippocampal cholinergic neurons alters memory-dependent
measures of brain connectivity without overt memory deficits.
Brayda-Bruno L(1), Mons N, Yee BK, Micheau J, Abrous DN, Nogues X, Marighetto A.
(1)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U862, F-33000 Bordeaux, France.
The functional relevance of septo-hippocampal cholinergic (SHC) degeneration to
the degradation of hippocampus-dependent declarative memory (DM) in aging and
Alzheimer’s disease (AD) remains ill-defined. Specifically, selective SHC lesions
often fail to induce overt memory impairments in animal models. In spite of
apparent normal performance, however, neuronal activity within relevant brain
structures might be altered by SHC disruption. We hypothesized that partial SHC
degeneration may contribute to functional alterations within memory circuits
occurring in aging before DM decline. In young adult mice, we studied the effects
of behaviorally ineffective (saporin-induced) SHC lesions – similar in extent to
that seen in aged animals – on activity patterns and functional connectivity
between three main neural memory systems: the septo-hippocampal system, the
striatum and the amygdala that sustain declarative, procedural and emotional
memory, respectively. Animals were trained in a radial maze procedure
dissociating the human equivalents of relational/DM and non-R/DM expressions in
animals. Test-induced Fos activation pattern revealed that the partial SHC lesion
significantly altered the brain’s functional activities and connectivity
(co-activation pattern) despite the absence of overt behavioral deficit.
Specifically, hippocampal CA3 hyperactivity and abnormal
septo-hippocampo-amygdalar inter-connectivity resemble those observed in aging
and prodromal AD. Hence, SHC neurons critically coordinate hippocampal function
in concert with extra-hippocampal structures in accordance with specific mnemonic
demand. Although partial SHC degeneration is not sufficient to impact DM
performance by itself, the connectivity change might predispose the emergence of
subsequent DM loss when, due to additional age-related insults, the brain can no
longer compensate the holistic imbalance caused by cholinergic loss.
Copyright © 2013 Elsevier Inc. All rights reserved.
PMID: 23376311 [Indexed for MEDLINE]