Abstract
Background
Cannabinoid receptor transmission strongly influences emotional processing, and disturbances
in cannabinoid signaling are associated with various neuropsychiatric disorders. The
mammalian ventral hippocampus (vHipp) is a critical neural region controlling mesolimbic
activity via glutamatergic projections to the nucleus accumbens. Furthermore, vHipp
abnormalities are linked to schizophrenia-related psychopathology. Nevertheless, the
mechanisms by which intra-vHipp cannabinoid signaling may modulate mesolimbic activity
states and emotional processing are not currently understood.
Methods
Using an integrative combination of in vivo electrophysiological recordings and behavioral
pharmacologic assays in rats, we tested whether activation of cannabinoid type 1 receptors
(CB1R) in the vHipp may modulate neuronal activity in the shell subregion of the nucleus
accumbens (NASh). We next examined how vHipp CB1R signaling may control the salience of rewarding or aversive emotional memory formation
and social interaction/recognition behaviors via intra-NASh glutamatergic transmission.
Results
We demonstrate for the first time that vHipp CB1R transmission can potently modulate NASh neuronal activity and can differentially
control the formation of context-dependent and context-independent forms of rewarding
or aversion-related emotional associative memories. In addition, we found that activation
of vHipp CB1R transmission strongly disrupts normal social behavior and cognition. Finally, we
report that these behavioral effects are dependent upon intra-NASh alpha-amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid/N-methyl-D-aspartate receptor transmission.
Conclusions
Together, these findings demonstrate a critical role for hippocampal cannabinoid signaling
in the modulation of mesolimbic neuronal activity states and suggest that dysregulation
of CB1R transmission in the vHipp→NASh circuit may underlie hippocampal-mediated affective
and social behavioral disturbances present in neuropsychiatric disorders.
Keywords
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Article info
Publication history
Published online: October 30, 2015
Accepted:
October 16,
2015
Received in revised form:
October 16,
2015
Received:
March 13,
2015
Identification
Copyright
© 2016 Society of Biological Psychiatry.
