The relevance of developmental and genetic studies in animals to the neurobiology of psychiatric disorders.

Abstract

The major goal of psychobiological research is to understand the neural and genetic mechanisms involved in the pathogenesis of psychiatric disorders. In recent years, developmental, neurobiological and molecular biological approaches have been used to investigate substrates of behavior in animals. Examples of innate or instinctual behavior, such as cowering before predator images, aggressive or reproductive responses to abdominal coloration, have in common a determined time course following triggering by stimulus. These 'modal action patterns' may have analogies with more complex human behaviors which are highly stereotyped. Many apparently innate behavior patterns have an experiential component, for example, imprinting or song development in birds. Birds are sexually differentiated as regards telencephalic regions which determine song. The example of alterations in occular dominance columns in the occipital cortex following eyelid suture at a critical development period illustrates the sensitivity of 'hard wired' neuronal systems to experiential factors. There are also examples of genetic determinants of behavioral expression. In Drosophila, a mutant has been discovered which develops hyperactive movement in response to exposure to ether anesthesia. This abnormal behavior has been shown to be associated with abnormal potassium conductance associated with a specific channel. The molecular determinants of learning have been studied in the gill and syphon withdrawal reflex of Aplysa. Short-term learning is associated with a change in a specific kinase which influences a voltage gated potassium conductance, leading to prolonged depolarization, enhanced calcium influx, leading in turn to augmented neurotransmitter release. Longer term learning depends on expression of specific mRNAs, and inhibitors of protein synthesis, administered at critical periods, disrupt the development of long-term memory. The author discusses the viability of passing from examples such as these to an eventual understanding of psychiatric disorders.