Differential timing for the appearance of neuronal and astrocytic beta-adrenergic receptors in the developing rat visual cortex as revealed by light and electron-microscopic immunocytochemistry.

Abstract

The developing cerebral cortex is likely to exhibit synaptic circuitries differing from those in adulthood, due to the asynchronous maturation of the various neurotransmitter systems. Two antisera directed against mammalian beta-adrenergic receptors (beta AR), beta AR248 and beta AR404, were used to characterize the laminar, cellular, and subcellular distributions of beta AR in postnatally developing visual cortex of rats. The antigenic sites were the receptor's third intracellular loop for beta AR248 and the C-terminus for beta AR404. During week 1, most of the beta AR404- and beta AR248-immunoreactive sites were dendritic. Morphologically identifiable synapses were rare, even in layer 1: yet, semiquantitative analysis revealed that beta AR404-immunoreactive synapses comprise half of those in layer 1. During week 2, the two antisera began to diverge in their immunoreactivity patterns. With beta AR248, there was an overall decline in immunoreactivity, while with beta AR404, there was an increase in immunoreactive sites, primarily due to labeled astrocytic processes that increased 200-fold in areal density by week 3. In contrast, the areal density of synaptic labeling by beta AR404 barely doubled, in spite of the 30-fold increase in areal density of synapses. These results suggest that beta AR undergo conformational changes during early postnatal periods, causing alterations in their relative antigenicity to the two antisera. Furthermore, the first 2 weeks appear to be characterized by modulation of earliest-formed synapses, and the subsequent phase is marked by addition of astrocytic responses that would be more diffuse temporally and spatially. Activation of beta AR is recognized to increase visually evoked activity relative to spontaneous activity. Moreover, astrocytic beta AR are documented to regulate extracellular concentrations of glutamate, ATP, and neurotrophic factors important for the formation of binocular connections. Thus, neuronal and astrocytic responses may, together and in tandem, facilitate strengthening of intracortical synaptic circuitry during early life.