Piriform cortex is an ictogenic trigger zone in the primate brain.

Objective: Area tempestas, a functionally defined region in the anterior piriform cortex, was identified as a crucial ictogenic trigger zone in the rat brain in the 1980s. However, whether the primate piriform cortex can trigger seizures remains unknown. Here, in a nonhuman primate model, we aimed to localize a similar trigger zone in the piriform cortex and, subsequently, evaluated the ability of focal inhibition of the substantia nigra pars reticulata (SNpr) to suppress the evoked seizures.

Focal pharmacological manipulation of serotonin signaling in the amygdala does not alter social behavior.

Serotonin signaling plays critical roles in social and emotional behaviors. Likewise, decades of research demonstrate that the amygdala is a prime modulator of social behavior. Permanent excitotoxic lesions and transient amygdala inactivation consistently increase social behaviors in non-human primates.

Pharmacological Inhibition of the Nucleus Accumbens Increases Dyadic Social Interaction in Macaques.

The nucleus accumbens (NAc) is a central component of the brain circuitry that mediates motivated behavior, including reward processing. Since the rewarding properties of social stimuli have a vital role in guiding behavior (both in humans and nonhuman animals), the NAc is likely to contribute to the brain circuitry controlling social behavior. In rodents, prior studies have found that focal pharmacological inhibition of NAc and/or elevation of dopamine in NAc increases social interactions.

Quinpirole, but not muscimol, infused into the nucleus accumbens disrupts prepulse inhibition of the acoustic startle in rhesus macaques.

Sensorimotor gating is the ability to suppress motor responses to irrelevant sensory inputs. This response is disrupted in a range of neuropsychiatric disorders. Prepulse inhibition (PPI) of the acoustic startle response (ASR) is a form of sensorimotor gating in which a low-intensity prepulse immediately precedes a startling stimulus, resulting in an attenuation of the startle response.

Pharmacological Inactivation of the Bed Nucleus of the Stria Terminalis Increases Affiliative Social Behavior in Rhesus Macaques.

The bed nucleus of the stria terminalis (BNST) has been implicated in a variety of social behaviors, including aggression, maternal care, mating behavior, and social interaction. Limited evidence from rodent studies suggests that activation of the BNST results in a decrease in social interaction between unfamiliar animals. The role of the BNST in social interaction in primates remains wholly unexamined.

Intrahippocampal blockade of nicotinic or muscarinic receptors fails to impair nonnavigational spatial memory in macaques.

Cholinergic neurotransmission within the hippocampus has long been suggested to play a pivotal role in memory processing, based partly on the assumption that the well-established amnestic effects of systemic cholinergic receptor blockade are mediated by the hippocampus. However, experimental evidence suggests that this may not be the case; a growing number of studies employing selective lesion or pharmacological approaches to disrupt cholinergic transmission within the hippocampus have failed to find robust deficits in either learning or memory, primarily in rodent models. Here, we evaluated the contribution of nicotinic acetylcholine receptor (nAChR)- and muscarinic acetylcholine receptor (mAChR)-mediated neurotransmission in the hippocampus of rhesus macaques for performance in a hippocampal-dependent spatial memory task, the Hamilton Search Task.

Inhibition of the Deep and Intermediate Layers of the Superior Colliculus Disrupts Sensorimotor Gating in Monkeys.

The deep and intermediate layers of the superior colliculus (DLSC) respond to visual, auditory, and tactile inputs and act as a multimodal sensory association area. In turn, activity in the DLSC can drive orienting and avoidance responses-such as saccades and head and body movements-across species, including in rats, cats, and non-human primates. As shown in rodents, DLSC also plays a role in regulating pre-pulse inhibition (PPI) of the acoustic startle response (ASR), a form of sensorimotor gating.

The Parahippocampal Cortex and its Functional Connection with the Hippocampus are Critical for Nonnavigational Spatial Memory in Macaques.

The Hamilton Search Task (HST) is a test of nonnavigational spatial memory that is dependent on the hippocampus. The parahippocampal cortex (PHC) is a major route for spatial information to reach the hippocampus, but the extent to which the PHC and hippocampus function independently of one another in the context of nonnavigational spatial memory is unclear. Here, we tested the hypotheses that (1) bilateral pharmacological inactivation of the PHC would impair HST performance, and (2) that functional disconnection of the PHC and hippocampus by contralateral (crossed) inactivation would likewise impair performance.

Dysregulation of behavioral and autonomic responses to emotional and social stimuli following bidirectional pharmacological manipulation of the basolateral amygdala in macaques.

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.

Colocalization of Tectal Inputs With Amygdala-Projecting Neurons in the Macaque Pulvinar.

Neuropsychological and neuroimaging studies have suggested the presence of a fast, subcortical route for the processing of emotionally-salient visual information in the primate brain. This putative pathway consists of the superior colliculus (SC), pulvinar and amygdala. While the presence of such a pathway has been confirmed in sub-primate species, it has yet to be documented in the primate brain using conventional anatomical methods.

Genetically Epilepsy-Prone Rats Display Anxiety-Like Behaviors and Neuropsychiatric Comorbidities of Epilepsy.

Epilepsy is associated with a variety of neuropsychiatric comorbidities, including both anxiety and depression. Despite high occurrences of depression and anxiety seen in human epilepsy populations, little is known about the etiology of these comorbidities. Experimental models of epilepsy provide a platform to disentangle the contribution of acute seizures, genetic predisposition, and underlying circuit pathologies to anxious and depressive phenotypes.

Inhibition of the substantia nigra pars reticulata produces divergent effects on sensorimotor gating in rats and monkeys.

The basal ganglia are an evolutionarily old group of structures, with gross organization conserved across species. Despite this conservation, there is evidence suggesting that anatomical organization of a key output nucleus of the basal ganglia, the substantia nigra pars reticulata (SNpr), diverges across species. Nevertheless, there are relatively few comparative studies examining the impact of manipulations of SNpr across species.

Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques.

Reward contingencies are dynamic: outcomes that were valued at one point may subsequently lose value. Action selection in the face of dynamic reward associations requires several cognitive processes: registering a change in value of the primary reinforcer, adjusting the value of secondary reinforcers to reflect the new value of the primary reinforcer, and guiding action selection to optimal choices. Flexible responding has been evaluated extensively using reinforcer devaluation tasks.

Effects of systemic cholinergic antagonism on reinforcer devaluation in macaques.

The capacity to adjust actions based on new information is a vital cognitive function. An animal's ability to adapt behavioral responses according to changes in reward value can be measured using a reinforcer devaluation task, wherein the desirability of a given object is reduced by decreasing the value of the associated food reinforcement. Elements of the neural circuits serving this ability have been studied in both rodents and nonhuman primates.

MRI Overestimates Excitotoxic Amygdala Lesion Damage in Rhesus Monkeys.

Selective, fiber-sparing excitotoxic lesions are a state-of-the-art tool for determining the causal contributions of different brain areas to behavior. For nonhuman primates especially, it is advantageous to keep subjects with high-quality lesions alive and contributing to science for many years. However, this requires the ability to estimate lesion extent accurately.

Defensive Vocalizations and Motor Asymmetry Triggered by Disinhibition of the Periaqueductal Gray in Non-human Primates.

Rapid and reflexive responses to threats are present across phylogeny. The neural circuitry mediating reflexive defense reactions has been well-characterized in a variety of species, for example, in rodents and cats, the detection of and species-typical response to threats is mediated by a network of structures including the midbrain tectum (deep and intermediate layers of the superior colliculus [DLSC]), periaqueductal gray (PAG), and forebrain structures such as the amygdala and hypothalamus. However, relatively little is known about the functional architecture of defense circuitry in primates.

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

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.

Development of relational memory processes in monkeys.

The present study tested whether relational memory processes, as measured by the transverse patterning problem, are late-developing in nonhuman primates as they are in humans. Eighteen macaques ranging from 3 to 36 months of age, were trained to solve a set of visual discriminations that formed the transverse patterning problem. Subjects were trained at 3, 4-6, 12, 15-24 or 36 months of age to solve three discriminations as follows: 1) A+ vs.

Bidirectional Control of Social Behavior by Activity within Basolateral and Central Amygdala of Primates.

Unlabelled: Both hypoactivity and hyperactivity in the amygdala are associated with perturbations in social behavior. While >60 years of experimental manipulations of the amygdala in animal models have shown that amygdala is critical for social behavior, many of these studies contradict one another. Moreover, several questions remain unaddressed.

Amygdala selectively modulates defensive responses evoked from the superior colliculus in non-human primates.

Brain circuitry underlying defensive behaviors includes forebrain modulatory sites, e.g. the amygdala and hypothalamus, and midbrain effector regions, such as the deep/intermediate layers of the superior colliculus (DLSC).

Effects of Separate or Combined Neonatal Damage to the Orbital Frontal Cortex and the Inferior Convexity on Object Recognition in Monkeys.

Unlike adult damage, neonatal damage to the inferior prefrontal convexity (IC) in monkeys spares learning and performance on the delayed nonmatching-to-sample (DNMS) task ( Málková et al. 2000). We investigated whether this sparing was due to compensation by undamaged orbital frontal cortex (O), an area also critical for DNMS, by comparing combined IC and O damage (Neo-ICO) with damage to O alone (Neo-O).