The morphogenesis of glutamic acid decarboxylase in the neostriatum of the cat: neuronal and ultrastructural localization

Abstract

Correlative light and electron microscopic immunohistochemical methods were adapted for a descriptive analysis of the normal time course and pattern of expression and intraneuronal localization of the enzyme glutamic acid decarboxylase (GAD) in the neostriatum (Ns) of fetal, postnatal and adult cats. The differentiation of this synthesizing enzyme demonstrated the establishment of γ-aminobutyric acid (GABA) transmitter identity in these neurons and their connections. The structural modifications of these GABAergic profiles revealed the morphogenesis of important inhibitory synaptic inputs in the Ns. The expression of GAD began during late fetal development and proceeded in a diagonal gradient from the first-formed ventrolateral putamen to the last-formed dorsomedial caudate nucleus. The frequency of GAD-positive elements increased with age particularly during the early postnatal period. After the initial expression of GAD, 3 interrelated processes contributed to its differentiation: (1) enzyme accumulation; (2) enzyme association with membranous organelles and (3) progressive elaboration of neuronal infrastructure. Synaptogenesis was both coincident and subsequent to GAD differentiation. Two principal types of GABAergic structures, cell bodies and axonal ‘terminals’, were evident from the initiation of GAD expression. The GABAergic cell bodies were polymorphic by and after the day of birth and consisted of ubiquitous medium sized cells (often having somatic and/or dendritic spines) and rare large sized cells (apparently aspiny and confined to a limited region of the Ns). The GABAergic axonal terminals changed from growth cone and prototerminal forms to mature bouton en passage and bouton terminaux forms establishing axosomatic and axodendritic contracts, having symmetric synaptic specializations and providing inputs to both medium- and large-sized GABAergic target neurons.