Bnip3 expression is strongly associated with reelin-positive entorhinal cortex layer II neurons

Abstract

In layer II of the entorhinal cortex, the principal neurons that project to the dentate gyrus and the CA3/2 hippocampal fields express the large glycoprotein reelin (Re+ ECLII-neurons). In rodents, neurons located at the dorsal extreme of the entorhinal cortex that thus border the rhinal fissure, express the highest levels, and the expression gradually decreases at levels successively further away from the rhinal fissure. Here we test two predictions following from the hypothesis that reelin expression is strongly correlated with neuronal metabolic rate. Since mitochondrial turnover rate serves as a proxy for energy expenditure, we predicted that the expression of the canonical promitophagic BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (Bnip3) would be upregulated in Re+ ECLII-neurons, and that the degree of upregulation would strongly correlate with the expression level of reelin in these neurons. We confirm both predictions, which implies that the energy requirement of Re+ ECLII-neurons is generally high, and that there is a systematic decrease in metabolic rate in these neurons as one moves successively away from the rhinal fissure. We tentatively suggest that the reasons for the high energy requirement of these neurons are their high rate of synaptic transmission and the high frequency by which they remold their synaptic contacts. This implies that the systematic variation in energy requirement of the neurons manifesting the observed reelin gradient ties in with the level of spatial and temporal detail by which they encode information about the external environment.