Abstract
Background
The nucleus accumbens (NAc) is a brain region implicated in pathological motivated
behaviors such as drug addiction and is composed predominantly of two discrete populations
of neurons, dopamine receptor-1– and dopamine receptor-2–expressing medium spiny neurons
(D1-MSNs and D2-MSNs, respectively). It is unclear whether these populations receive
inputs from different brain areas and whether input regions to these cell types undergo
distinct structural adaptations in response to the administration of addictive drugs
such as cocaine.
Methods
Using a modified rabies virus–mediated tracing method, we created a comprehensive
brain-wide monosynaptic input map to NAc D1- and D2-MSNs. Next, we analyzed nearly
2000 dendrites and 125,000 spines of neurons across four input regions (the prelimbic
cortex, medial orbitofrontal cortex, basolateral amygdala, and ventral hippocampus)
at four separate time points during cocaine administration and withdrawal to examine
changes in spine density in response to repeated intraperitoneal cocaine injection
in mice.
Results
D1- and D2-MSNs display overall similar input profiles, with the exception that D1-MSNs
receive significantly more input from the medial orbitofrontal cortex. We found that
neurons in distinct brain areas projecting to D1- and D2-MSNs display different adaptations
in dendritic spine density at different stages of cocaine administration and withdrawal.
Conclusions
While NAc D1- and D2-MSNs receive input from similar brain structures, cocaine-induced
spine density changes in input regions are quite distinct and dynamic. While previous
studies have focused on input-specific postsynaptic changes within NAc MSNs in response
to cocaine, these findings emphasize the dramatic changes that occur in the afferent
input regions as well.
Keywords
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Article info
Publication history
Published online: May 09, 2018
Accepted:
April 20,
2018
Received in revised form:
April 6,
2018
Received:
January 31,
2018
Identification
Copyright
Published by Elsevier Inc on behalf of Society of Biological Psychiatry.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Deconstructing and Reconstructing the Dichotomy That Is Dopamine Receptor-1– and Dopamine Receptor-2–Expressing NeuronsBiological PsychiatryVol. 84Issue 12
- PreviewThe last decade of technological advances in clinical and preclinical analysis of brain circuitry has created a consensus of high optimism in our research community for rapid advances in our working understanding of brain physiology. This is especially true regarding understanding how brain circuits mediate the execution of new and previously learned motivated behaviors. Since many psychiatric disorders are clinically described in part as harboring dysregulations in motivated behavior, there is parallel optimism that our technological advances in mapping the anatomy and function of brain circuits will significantly assist in identifying the pathophysiology of at least this endophenotype in psychiatric disorders.
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