Blockade of glutamatergic transmission in the primate basolateral amygdala suppresses active behavior without altering social interaction

Abstract

The amygdala is an integrator of affective processing, and a key component of a network regulating social behavior. While decades of lesion studies in nonhuman primates have shown alterations in social interactions after amygdala damage, acute manipulations of the amygdala in primates have been underexplored. We recently reported (Wellman, Forcelli, Aguilar, & Malkova, 2016) that acute pharmacological inhibition of the basolateral complex of the amygdala (BLA) or the central nucleus of the amygdala increased affiliative social interactions in experimental dyads of macaques; this was achieved through microinjection of a GABA-A receptor agonist. Prior studies in rodents have shown similar effects achieved by blocking NMDA receptors or AMPA receptors within the BLA. Here, we sought to determine the role of these receptor systems in the primate BLA in the context of social behavior. In familiar dyads, we microinjected the NMDA receptor antagonist 2-amino-7-phosphonoheptanoic acid (AP7) or the AMPA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) and observed behaviors and social interactions in the immediate postinjection period. In striking contrast with our prior report using GABA agonists, and in contrast with prior reports in rodents using glutamate antagonists, we found that neither NMDA nor AMPA blockade increase social interaction. Both treatments, however, were associated with decreases in locomotion and manipulation and increases in passive behavior. These data suggest that local blockade of glutamatergic neurotransmission in BLA is not the functional equivalent of local activation of GABAergic signaling, and raise interesting questions regarding the functional microcircuitry of the nonhuman primate amygdala in the context of social behavior. (PsycINFO Database Record

Figure 1

We found a close correspondence between histologically-verified infusion sites and those determined by MRI (see A and D for subject ZA and B and E for subject JA). Electrode tips were located within the basal, accessory basal, ventrobasal, and lateral subnuclei of the amygdala. (A) Infusion site for ZA (symbols match those used in Figs 2 and 3), (B) Infusion sites for JA, (C) Infusion sites for ZA. (D and E) MRI showing electrodes tips placed dorsal to the intended infusion site. Arrows indicate cannula tip (A–C) or electrode tip (D-E). Dotted line in E indicates the intended extension from the original electrode artifact. (F) Schematic showing the intended infusion region (shaded) encompassing the basal nuclei and the lateral nucleus. Symbols indicate positions of infusions.

Figure 2. NMDA or AMPA receptor antagonists in BLA increase passive and decrease active behaviors

(A) Passive behavior, as defined in Table 1, under baseline, AP7 infused or NBQX infused conditions. (B) Manipulation (as defined in Table 1). (C) Locomotion (as defined in Table 1). Symbols indicate the mean (+SEM) value for each animal. Bars show group means + SEM. * = significantly different than baseline, P<0.05, Sidak-corrected.

Figure 3. Effect of NMDA or AMPA blockade in BLA on social behaviors

(A) Total contact (as defined in Table 1); while the main effect of treatment for this behavior approached, but did not reach statistical significance, comparison between AP7 and Baseline sessions revealed a decrease in contact after AP7 infusion (P<0.05) (B) Play behavior (C) Approach, (D) Grooming and (E) Soliciting Grooming. Symbols follow the conventions in Figs 1 and 2. Symbols indicate the mean (+SEM) value for each animal. Bars show group means + SEM. * = significantly different than baseline, P<0.05, Sidak-corrected.