Pharmacological agents and electrophysiological techniques

Abstract

Pharmacological and electrophysiological study of hemispheric asymmetry has been particularly fruitful in systems in which anatomical, physiological, and behavioral asymmetries are readily demonstrated. In the domestic chick, several behavioral phenomena meet these conditions, including the learning processes of filial imprinting and passive avoidance learning. The chick possesses special advantages for studies of this kind, such as a wide range of readily measured behaviors, a highly permeable blood–brain barrier and amenability to strict control of the developmental environment. Moreover, modification of the visual environment during embryonic development can produce hemispheric asymmetry in visual pathways. A restricted region of the chick forebrain, the intermediate and medial mesopallium (IMM), has been shown to be a memory region, and shows marked functional hemispheric asymmetry during learning and memory processing. Whenever hemispheric asymmetry in the control of behavior is being sought, significant statistical interaction of experimental treatment with side is generally required for a secure inference of lateralization. When drugs are directly applied to brain tissue, topographical spread may be measured directly, or inferred from diffusion models and drug application at control sites; the effects of systemic injections may be estimated using pharmacokinetic modeling and local or systemic application of agonists and antagonists. A whole hemisphere may be inactivated reversibly by intra-carotid injection of anesthetic. Many commissural projection neurons are glutamatergic, allowing inter-hemispheric communication to be modified by intra-cerebral application of appropriate drugs. Much behavior in the chick has been shown pharmacologically (e.g. by activating or blocking glutamate receptors) to be under asymmetrical control, including visual discrimination, auditory habituation, copulation, and attack behavior, as well as behavior resulting from learning and memory associated with imprinting and passive avoidance learning. Learning- and memory-related hemispheric symmetries have been found in neuronal activity and neurotransmitter systems in the IMM. Neural systems participating in birdsong have long been known to exhibit hemispheric asymmetry and this is reflected in neuronal activity and sensitivity to electrical stimulation. Hemispheric asymmetry in olfactory pathways has been found in mammals and birds, and has been investigated pharmacologically and electrophysiologically. The study of hemispheric asymmetry is likely to be enhanced by specific pharmacological targeting of proteins and nucleic acids and increasingly specific drug design, complemented by electrophysiological analysis.