Medial septal cholinergic neurons are necessary for context‐place memory but not episodic‐like memory

Abstract

Loss of cholinergic cortical input is associated with diseases in which episodic memory impairment is a prominent feature, but the degree to which this neurochemical lesion can account for memory impairment in humans with neurodegenerative diseases remains unclear. Removal of cholinergic input to hippocampus impairs some of its functions in memory, perhaps by reducing the plasticity of information representation within the hippocampus, but the role of cholinergic hippocampal input in episodic-like memories has not been investigated. To address this question, we tested rats with selective lesions of basal forebrain neurons in the medial septum and vertical limb of the diagonal band (MS/VDB), which contains hippocampal-projecting cholinergic neurons, on a task of integrated memory for objects, places, and contexts ("what-where-which" memory). This task serves as a rodent model of human episodic memory (episodic-like memory) and is sensitive to damage to the hippocampal system. Rats with lesions of cholinergic MS/VDB neurons performed as well on the what-where-which task as controls, but were impaired in a task that simply required them to associate places with contexts ("where-which" memory). Thus, episodic-like memories that rely on the hippocampus do not require cholinergic neuromodulation to be formed. Nevertheless, some more specific aspects of where-which memory, which may be more dependent on the plasticity of hippocampal spatial representations, require acetylcholine. These results suggest that cholinergic projections to hippocampus are not necessary for episodic memory and, furthermore, that hippocampal spatial representations may be to some extent dissociable from episodic memory function.

The episodic nature of episodic-like memories

“…This strengthens the conclusions drawn from use of this task with nonhuman populations (e.g., Eacott and Norman 2004;Langston and Wood 2010;Easton et al 2011; KE Davis, A Easton, MJ Eacott, J Gigg, in prep.). Moreover, as a recognition memory task, it can be simply adapted to provide a comparable test of episodic memory for use with humans, including other nonverbal populations such as human infants (cf.…”

Incidental context information increases recollection

“…Rather than recollection being for the associations between the individual components, it may instead be recollection for the "scene" or "snapshot" at the time of the event, and that this "scene" is much more than the sum of its parts (Gaffan 1992(Gaffan , 1994). This interpretation is in line with studies of OLC memory in animals, showing that this type of memory is quantitatively different from memory for individual or pairs of components (Gaffan 1994;Eacott and Norman 2004;Eacott and Gaffan 2005;Norman and Eacott 2005;Easton et al 2011).In summary, manipulating incidental information at retrieval produces a step-wise change in the ROC curve only when all of object, location, and context are congruent with their presentation at encoding. This change does not occur in a linear manner with the addition of recall cues, but instead represents a shift only in the OLC condition.…”

Cholinergic modulation of event-related oscillations (ERO)

“…In general, NBM lesions have shown to impair performance on a variety of tasks involving sustained attention and discrimination (Dunnett, 1991; Harati et al, 2008; Lehmann et al, 2003; Motohashi et al, 1986; Nieto-Escamez et al, 2002; Risbrough et al, 2002; Santucci and Haroutunian, 1989). Lesions of medial septum impair learning and memory and generation of hippocampal theta rhythm (Brito and Brito, 1990; Colom et al, 1991; Easton et al, 2011; Harati et al, 2008; Martin et al, 2008). The cholinergic innervation of the hippocampus plays a key role in spatial reference memory processes involved in place navigation (Hagan et al, 1988) and rats with lesions of cholinergic medial septum are impaired in a task that requires the association of places with contexts (Easton et al, 2011).…”

“…Lesions of medial septum impair learning and memory and generation of hippocampal theta rhythm (Brito and Brito, 1990; Colom et al, 1991; Easton et al, 2011; Harati et al, 2008; Martin et al, 2008). The cholinergic innervation of the hippocampus plays a key role in spatial reference memory processes involved in place navigation (Hagan et al, 1988) and rats with lesions of cholinergic medial septum are impaired in a task that requires the association of places with contexts (Easton et al, 2011). Combined lesions in the medial septum/diagonal band and nucleus basalis magno-cellularis (NBM) in rats induces spatial memory impairment (Waite et al, 1994) which is qualitatively similar to nucleus basalis lesions alone involving decreasing of the attentional load (Lehmann et al, 2003).…”