Amygdalar GABAergic-rich neural grafts attenuate anxiety-like behavior in rats.
Transplantation experiments have shown that neurologic deficits may be reversed by engrafting fresh tissue or engineered cells within dysfunctional neural circuitry. In experimental and clinical settings, this approach has provided insights into the pathology and treatment of neurologic diseases, primarily movement disorders. The present experiments were designed to investigate whether a similar strategy is feasible as a method to investigate, and perhaps repair, circuitry integral to emotional disorders. We focused on the amygdala, a macrostructure known to be involved in the expression of anxiety- and fear-related behaviors. GABAergic cell-rich suspensions were prepared from E17 rat lateral ganglionic eminence and engrafted bilaterally into the lateral and basolateral amygdaloid nuclei of young adult rats. After 6 weeks, increased numbers of GABAergic neurons were identified in the vicinity of the graft sites, and electron microscopy provided evidence for functional integration of transplanted cells. Rats with these grafts spent more time in the open arms of the elevated-plus maze, consistent with an anxioloytic-like phenotype. These rats were also less sensitive to the unconditioned anxiogenic effects of light on the acoustic startle response, although fear-potentiated startle was not affected, suggesting that the grafts produced an attenuation of unlearned fear but did not affect acquisition of conditioned fear. Our results raise the possibility that distinct components of emotion can be modulated by strategic neural engraftment.
Cunningham
Miles Gregory
MG
Laboratory for Neural Reconstruction, McLean Hospital, Program in Neuroscience and Department of Psychiatry, Harvard Medical School, Boston, MA 02478, USA. mcunningham@mclean.harvard.edu
Connor
Caroline Martine
CM
Carlezon
William A
WA
Meloni
Edward
E
D000679:Amygdala / Q000503:physiopathology / Q000601:surgery* / Q000648:ultrastructure; D000818:Animals; D001008:Anxiety Disorders / Q000503:physiopathology / Q000601:surgery* / Q000628:therapy; D001307:Auditory Perception / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D016380:Brain Tissue Transplantation; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D016332:Fetal Tissue Transplantation; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000637:transplantation* / Q000648:ultrastructure; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000502:physiology; D014796:Visual Perception / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid