The role of basal forebrain cholinergic projections to the anterior cingulate cortex in cued and contextual fear conditioned suppression paradigms
Date
2017
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Basal forebrain corticopetal cholinergic neurons are critical for contextual and
cued fear memory in the conditioned suppression paradigm, but neural mechanisms
that alter these neurons in fear memory remain unknown. Interestingly, basal forebrain
cholinergic lesions have no effect on behavioral performance in commonly-studied
fear conditioning paradigms like Pavlovian conditioned freezing or fear-potentiated
startle, yet impair fear memory in the conditioned suppression paradigm. Many studies
conducted have experimented with lesions of cell bodies of corticopetal cholinergic
neurons in the nucleus basalis magnocellularis (NBM), but there is a void in the
literature defining which specific projections may be responsible for their discrepant
role in different fear memory paradigms. The basal forebrain projects to the anterior
cingulate cortex (ACC), a subregion of the medial prefrontal cortex. The ACC is a
well-established portion of the fear circuit across all fear conditioning paradigms and
has a clear role in decision-making in the conditioned suppression paradigm. Given
the role in choice conflict that the ACC plays in operant tasks involved in the
conditioned suppression paradigm, it is plausible that it may be a region that allows
basal forebrain cholinergic neurons to alter a fear memory in the conditioned
suppression paradigm. The goal of this study is to examine the specific roles that basal
forebrain cholinergic projections to the ACC play in fear memory, specifically in the
conditioned suppression paradigm. These lesions may target specific cholinergic input
to the ACC from the NBM in the basal forebrain and this may isolate a specific fear
circuit involved in fear memory in the conditioned suppression paradigm. Data have
suggested that ACC lesioned animals demonstrate less fear-conditioned suppression
over sham animals, but further experiments and cohorts of animals are required. If
ACC cholinergic lesions are shown to produce deficits in fear memory in the
conditioned suppression paradigm, it may suggest that the presence of the appetitive
task, which only occurs in the conditioned suppression paradigm and not in any of the
other commonly studied fear paradigms, may be able to elicit changes in functional
connectivity to incorporate this projection from the NBM to the ACC to the fear
circuit. Discrepancies in fear memory between fear conditioning paradigms demand to
be addressed because assumptions about functional connectivity across different
paradigms are assumed to be similar in the literature. If the notion of paradigmdependent
functional connectivity presented here is true, deductions about this
functional connectivity may only be made in the context of one fear paradigm and
may not necessarily be applicable across paradigms. In other words, to say that
Pavlovian fear conditioning and fear-potentiated startle are indicative of the broad
neurobiology of fear memory would only be looking at a fraction of the reality behind
how fear circuitry operates. In order to further the literature to propose holistic
circuits, molecular processes and constructs that apply to all fear memory regardless of
protocol or paradigm, it is necessary to investigate neural involvement across
alternative fear paradigms, like conditioned suppression. This study supports the novel
idea that neural circuitry that supports fear can expand with new learning tasks or
events and therefore, may be more susceptible to change than previously considered,
but future studies are required.
Description
Keywords
Biological sciences, Psychology, ACC, Anxiety, Basal forebrain, Cholinergic, Conditioned suppression, NBM