TY - JOUR
T1 - Dysregulation of behavioral and autonomic responses to emotional and social stimuli following bidirectional pharmacological manipulation of the basolateral amygdala in macaques
AU - Elorette, Catherine
AU - Aguilar, Brittany L.
AU - Novak, Vera
AU - Forcelli, Patrick A.
AU - Malkova, Ludise
N1 - Funding Information:
This work was funded by the National Institutes of Health ( R01MH099505 to LM and R01 MH120638 to LM and PF). CE was supported by the National Institutes of Health ( T32NS041231 ). PF received support from the National Institutes of Health ( KL2TR001432 ). BA was supported by the National Institutes of Health ( T32NS041218 , T32NS041231 , and R01NS0977762–01S1 ). The authors declare no conflict of interest. We thank the Malkova and Forcelli laboratories for help with infusions and surgeries and Dr. Patricia Foley for assistance with telemetry implantation.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/11/15
Y1 - 2020/11/15
N2 - The amygdala is a key component of the neural circuits mediating the processing and response to emotionally salient stimuli. Amygdala lesions dysregulate social interactions, responses to fearful stimuli, and autonomic functions. In rodents, the basolateral and central nuclei of the amygdala have divergent roles in behavioral control. However, few studies have selectively examined these nuclei in the primate brain. Moreover, the majority of non-human primate studies have employed lesions, which only allow for unidirectional manipulation of amygdala activity. Thus, the effects of amygdala disinhibition on behavior in the primate are unknown. To address this gap, we pharmacologically inhibited by muscimol or disinhibited by bicuculline methiodide the basolateral complex of the amygdala (BLA; lateral, basal, and accessory basal) in nine awake, behaving male rhesus macaques (Macaca mulatta). We examined the effects of amygdala manipulation on: (1) behavioral responses to taxidermy snakes and social stimuli, (2) food competition and social interaction in dyads, (3) autonomic arousal as measured by cardiovascular response, and (4) prepulse inhibition of the acoustic startle (PPI) response. All modalities were impacted by pharmacological inhibition and/or disinhibition. Amygdala inhibition decreased fear responses to snake stimuli, increased examination of social stimuli, reduced competitive reward-seeking in dominant animals, decreased heart rate, and increased PPI response. Amygdala disinhibition restored fearful response after habituation to snakes, reduced competitive reward-seeking behavior in dominant animals, and lowered heart rate. Thus, both hypoactivity and hyperactivity of the basolateral amygdala can lead to dysregulated behavior, suggesting that a narrow range of activity is necessary for normal functions.
AB - The amygdala is a key component of the neural circuits mediating the processing and response to emotionally salient stimuli. Amygdala lesions dysregulate social interactions, responses to fearful stimuli, and autonomic functions. In rodents, the basolateral and central nuclei of the amygdala have divergent roles in behavioral control. However, few studies have selectively examined these nuclei in the primate brain. Moreover, the majority of non-human primate studies have employed lesions, which only allow for unidirectional manipulation of amygdala activity. Thus, the effects of amygdala disinhibition on behavior in the primate are unknown. To address this gap, we pharmacologically inhibited by muscimol or disinhibited by bicuculline methiodide the basolateral complex of the amygdala (BLA; lateral, basal, and accessory basal) in nine awake, behaving male rhesus macaques (Macaca mulatta). We examined the effects of amygdala manipulation on: (1) behavioral responses to taxidermy snakes and social stimuli, (2) food competition and social interaction in dyads, (3) autonomic arousal as measured by cardiovascular response, and (4) prepulse inhibition of the acoustic startle (PPI) response. All modalities were impacted by pharmacological inhibition and/or disinhibition. Amygdala inhibition decreased fear responses to snake stimuli, increased examination of social stimuli, reduced competitive reward-seeking in dominant animals, decreased heart rate, and increased PPI response. Amygdala disinhibition restored fearful response after habituation to snakes, reduced competitive reward-seeking behavior in dominant animals, and lowered heart rate. Thus, both hypoactivity and hyperactivity of the basolateral amygdala can lead to dysregulated behavior, suggesting that a narrow range of activity is necessary for normal functions.
KW - Amygdala
KW - Approach-avoid
KW - Heart rate
KW - Non-human primate
KW - PPI
KW - Social
UR - http://www.scopus.com/inward/record.url?scp=85090160881&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2020.108275
DO - 10.1016/j.neuropharm.2020.108275
M3 - Article
C2 - 32835765
AN - SCOPUS:85090160881
SN - 0028-3908
VL - 179
JO - Neuropharmacology
JF - Neuropharmacology
M1 - 108275
ER -