Calbindin immunoreactivity in the geniculo-extrastriate system of the macaque: implications for heterogeneity in the koniocellular pathway and recovery from cortical damage.

Although most projection neurons in the primate dorsal lateral geniculate nucleus (dLGN) target striate cortex (V1), a small number project instead to extrastriate visual areas and have been suggested to play a role in the preserved vision ("blindsight") that survives damage to V1. Moreover, the distribution of dLGN cells projecting to extrastriate bears a striking similarity to that of neurons that stain for calbindin D-28K (Cal), a calcium-binding protein involved in regulating neuronal excitability and considered a marker for the koniocellular or "K" pathway of geniculocortical processing. In these studies, we used double-labeling techniques to examine whether Cal content characterizes all or a subset of neurons making up the geniculo-extrastriate pathway in normal macaque monkeys. After injections of cholera toxin B-subunit into the prelunate gyrus, the proportion of retrogradely labeled neurons in the dLGN that were also immunoreactive for Cal varied from less than 40% to over 80%, indicating that only a subset of the geniculo-extrastriate projection falls within the K pathway as defined by Cal content. Analysis of the injected territories indicated that identity of the extrastriate cortical target may be systematically related to Cal content in the geniculo-extrastriate projection. To see whether the Cal-immunoreactive dLGN population might potentially play a role in preserved vision after V1 damage, we also examined the dLGN of a macaque that had sustained a lesion of V1 in infancy and survived until 4 years. In this animal, large, intensely Cal-immunoreactive neurons were found scattered throughout the otherwise degenerated dLGN zones and made up over 95% of the identifiable remaining neurons. The results support an emerging view that the macaque koniocellular system is highly heterogeneous in nature and also suggest that Cal content may be a critical feature of the pathway by which visual information reaches extrastriate cortex in the absence of V1.

Sex difference in the phosphorylation of cAMP response element binding protein (CREB) in neonatal rat brain.

On the day of birth, a surge in testicular testosterone release in male rats is critical for sexual differentiation of the brain. Steroid hormones function by binding to intracellular steroid receptors and altering gene expression; however, little is known about the signal transduction pathways altered as a consequence of steroid hormone action in developing brain. We investigated whether the increase in testosterone at birth alters the phosphorylation of CREB, a major signal transduction protein. Adjacent brain sections from male and female pups were immunocytochemically stained for serine(133) phosphorylated CREB (pCREB) or total CREB on the day of birth. Males had more pCREB-immunoreactive positive cells than females in the medial preoptic area, ventromedial nucleus of the hypothalamus, the arcuate nucleus, and the CA1 region of the hippocampus, but not in two thalamic nuclei. There was no sex difference in total CREB immunoreactive cell number. To determine if the sex difference in pCREB persisted 24 h after birth and whether the difference was due to testosterone, newborn female pups were injected with 100 microg of testosterone propionate, and male and control female pups were injected with vehicle. Twenty-four hours later, adjacent brain sections were immunocytochemically stained for either pCREB or CREB. We found that males and testosterone-treated females had more pCREB in the ventromedial nucleus of the hypothalamus contrasted to control females. There were no group differences in pCREB or CREB in any other area examined. These results indicate that some of the effects of testosterone in developing brain occur via pathways associated with the phosphorylation of CREB.