Midbrain Contributions to Innate Defense and Anxiety Behaviors

Abstract

The central nervous system (CNS) comprises the necessary components for converting sensation into behavior, a phenomenon fundamental to mammalian survival. One way that sensation can be converted into behavior is via a reflex: an automatic motoric response to an external stimulus. Unconditioned reflexes like startle response are mediated by the spinal cord and brainstem. However, responses may be modified by descending cortical and subcortical pathways, the mechanism of which remains poorly understood particularly across species. This dissertation summarizes a three-pronged approach to rendering clearer the nature of midbrain modulation of reflexes and related defensive behaviors.

First, I investigated midbrain structure contributions to modulation of the auditory startle response, in rats and macaques. Here, I show a species-specific divergence in functional contributions of the substantia nigra pars reticulata (SNpr) to prepulse inhibition (PPI) of the auditory startle reflex (ASR). I explain this divergent behavior by consolidating what is known about anatomical projections of involved structures in both rats and macaques. Following this, I explored contributions of basolateral amygdala (BLA) and accessory basal nucleus of the amygdala (AB) to PPI in both species.

Next, I observed how genetically inherited changes in midbrain structures may influence unconditioned anxiety-like behavior in the genetically epileptic prone rat (GEPR-3). The behavioral studies presented here demonstrate a rich anxiety-like phenotype. I conclude that the emergence of these behaviors prior to onset of seizures suggests a common etiology underlying both behavioral changes and seizure susceptibility.

Finally, I piloted use of designer receptors exclusively activated by designer drugs (DREADDs) in intermediate and deep layers of the superior colliculus (DLSC) in an attempt to alter threat response in monkeys. No behavioral changes were observed, but progress was made in methodological development of DREADD use in macaques.

In addition to the divergent anatomy underlying PPI results, an understanding of species specificity was crucial for development of the looming threat test in rats and interpretation of the elaborate responses elicited during the Human Intruder test in macaques (a behavior not reported in rodents). I therefore demonstrate the importance of cross-species studies in understanding basic structural contributions to behavior.