Theoretical models of information storage in the brain have suggested that neurons may undergo an experience-dependent tuning or sharpening of their representations in order to maximize the amount of information that can be stored. Changes in the tuning profiles of neurons have been demonstrated to occur when animals must learn perceptual discriminations, however, whether similar changes occur in the absence of behavioral demands is unclear. To address these questions, the activity of simultaneously recorded medial temporal lobe (MTL) neurons was studied in relation to a passive visual recognition memory task. The structure of this task was such that it allowed for a comparison between novelty related responses as well as tuning properties of individual neurons. A total of 565 well isolated single neurons were recorded. The first contribution of this dissertation is the finding of a dissociation between different medial temporal lobe regions such that neurons in temporal area F (TF), but not perirhinal cortex (PRC) or the hippocampus, show an experience-dependent change in their stimulus selectivity. This finding indicates that tuning of stimulus representations may be an effective mechanism for maximizing information storage in some brain regions. The absence of stimulus tuning in higher level association regions (i.e. TF and PRC) suggests that tuning in these regions may be disadvantageous due to the need to construct unified representations across sensory modalities. A complimentary question to the question of network storage capacity is how networks avoid saturation in the connections between neurons. The second contribution of this dissertation is the finding that there exists a decrease in the magnitude of the short time scale correlations between pairs of neurons; suggesting that networks reduce the number of connections between neurons as a stimulus becomes familiar. Gamma oscillations have been proposed to be the mechanism by which groups of neurons coordinate their activity. However, network coordination has only been indirectly measured. The final contribution of this dissertation is the finding that the magnitude of gamma oscillations is strongly correlated with enhanced magnitude of correlations between neurons.

Eye contact is a fundamental means of social interaction among primates. In both humans and non-human primate societies, eye contact precedes and signals aggression or prosocial behaviors. Initiating and maintaining short periods of eye contact is essential during social interactions that build trust and promote cooperation. How the brain detects and orchestrates social exchanges mediated by eye contact remains an open question in neuroscience. Theories of social neuroscience speculate that the social brain in primates contains neurons specialized to detect and respond to eye-contact. This dissertation reports the discovery and characterization of a class of neurons, located in the amygdala of monkeys, that is activated selectively during eye contact. The discovery of these cells was facilitated by (1) characterization of the response properties of neurons in the amygdala during a canonical image-viewing task and (2) development of a reliable and quantifiable method for eliciting naturalistic eye contact between monkeys in the laboratory setting. The functional role of eye contact cells remains to be determined. The data presented in this dissertation confirm the role of the amygdala in social behaviors and allows for the formulation of new hypotheses about the cellular mechanisms within the amygdala that support complex social interactions among primates.

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Detecting and interpreting sensory events, and remembering those events in in the service of future actions, forms the foundation of all behavior. Each of these pillars of the so-called "perception-action cycle" have been topics of extensive inquiry throughout recorded history, with philosophical foundations provided by early BCE and CE periods (especially during the Classic and Renaissance eras) leading to intensive empirical study in the twentieth and twenty-first centuries. Such experiments have described detailed (but incomplete) behavioral functions reflecting perception and memory, and have begun to unravel the extraordinarily complex substrates of these functions in the nervous system. The current dissertation was motivated by these findings, with the goal of meaningfully extending our understanding of such processes through a multi-experiment approach spanning the behavioral and neurophysiological levels. The focus of these experiments is on short-term memory (STM), though as we shall see, STM is ultimately inseparable from sensory perception and is directly or indirectly associated with guidance of motor responses. It thus provides a nexus between the sensory inputs and motor outputs that describe interactions between the organism and environment. In Chapter 2, previous findings from nonhuman primate literature describing relatively poor performance for auditory compared to visual or tactile STM inspired similar comparisons among modalities in humans. In both STM and recognition memory paradigms, accuracy is shown to be lowest for the auditory modality, suggesting commonalities among primate species. Chapters 3-5 examined STM processing in nonhuman primates at the behavioral and neurophysiological levels. In Chapter 3, a systematic investigation of memory errors produced by recycling memoranda across trials (proactive interference) is provided for the understudied auditory modality in monkeys. Such errors were ameliorated (but not completely eliminated) by increasing the proportions of unique memoranda presented within a session, and by separating successive trials by greater time intervals. In Chapter 4, previous results revealing a human memory advantage for audiovisual events (compared to unimodal auditory or visual events) inspired a similar comparison in monkeys using a concurrent auditory, visual, and audiovisual STM task. Here, the primary results conformed to a priori expectations, with superior performance observed on audiovisual trials compared to either unimodal trial type. Surprisingly, two of three subjects exhibited superior unimodal performance on auditory trials. This result contrasts with previous results in nonhuman primates, but can be interpreted in light of these subjects' extensive prior experience with unimodal auditory STM tasks. In Chapter 5, the same subjects performed the concurrent audiovisual STM task while activity of single cells and local cell populations was recorded within prefrontal cortex (PFC), a region known to exhibit multisensory integrative and memory functions. The results indicate that both of these functions converge within PFC, down to the level of individual cells, as evidenced by audiovisual integrative responses within mnemonic processes such as delay-related changes in activity and detection of repeated versus different sensory cues. Further, a disproportionate number of the recorded units exhibited such mnemonic processes on audiovisual trials, a finding that corresponds to the superior behavioral performance on these trials. Taken together, these findings reinforce the important role of PFC in STM and multisensory integration. They further strengthen the evidence that "memory" is not a unitary phenomenon, but can be seen as the outcome of processing within and among multiple subsystems, with substantial areas of overlap and separation across modalities. Finally, cross-species comparisons reveal substantial similarities in memory processing between humans and nonhuman primates, suggesting shared evolutionary heritage of systems underlying the perception-action cycle.

Introduction: major depressive disorder is a common psychiatric disorder associated with high economic cost, severe human suffering, and low remission rates. Imbalanced neurotransmission of the monoaminergic serotonin (5-HT), dopamine (DA) and norepinephrine (NE) systems is implicated in this disorder. However, the etiology underlying this presumed imbalance and the mechanism by which antidepressant strategies restore this imbalance requires further exploration. Accordingly, the present work assessed the effects of depressogenic and antidepressant-like conditions on these systems. Methodology: Electrophysiological extracellular single unit recordings from 5-HT, DA, NE, and hippocampal pyramidal neurons were obtained in adult male chloral hydrate anaesthetized Sprague-Dawley rats. Effects on relevant receptors were characterized using established electrophysiological and/or pharmacological strategies. Prenatal stress was used to model depressogenic-like conditions. The effects on monoamine systems of asenapine and brexpiprazole, two atypical antipsychotics with antidepressant potential, were characterized after acute (brexpiprazole) and sustained administration. These sustained regimens resulted in clinically relevant blood plasma levels. Results: Prenatal stress exposure altered monoamine system activities but did not produce detrimental effects on behavior. Asenapine and brexpiprazole had unique effects on the activities of monoamine systems. Unlike other antipsychotics, both agents did not produce a cessation of the firing of dopamine neurons in the ventral tegmental area, thereby providing novel insights in the role of this system in the treatment of mood disorders. Furthermore, both agents enhanced the tonic activation of postsynaptic 5-HT1A receptors, similarly to the effects of all antidepressant strategies. Conclusion: Prenatal stress altered the activities of 5-HT, NE and DA neurons. Since these central changes were obtained in animals displaying normal behavior, they presumably reflect adaptations to depressogenic-like conditions. The characterization of asenapine and brexpiprazole contributed to a further understanding of their mechanisms of action. Together, these studies provide insight in neural substrates presumably relevant to the antidepressant response.

ABTRACT In order to survive, an animal must be able to integrate vital information about it's surroundings, such as information about the environment and the social interactions therein. Decades of research have established the hippocampal formation as a structure indispensable for spatial memory. It was only recently, though, that evidence has emerged suggesting that the hippocampus, most notably the dorsal CA2 region, also supports the encoding of social information. New behavioural as well as electrophysiological evidence appeared, highlighting the importance of sleep for the processing of social information. In my thesis, I used microelectrodes to record the electrophysiological activity of individual CA2 neurons from freely-moving rats, during wake as well as in sleep. In order to study the processing of social information by hippocampal neurons, I employed a novel experimental paradigm in which social stimulation, in the form of two rat conspecifics, was presented in a spatial context. I report that the discharge of some CA2 neurons was organised within the experimental maze, even after social stimulation was added. Moreover, I observed that the spatial activity of neurons changed after the addition of social stimuli, and that it further changed when the location of the two conspecifics was shuffled....

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