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Development of piriform cortex interhemispheric connections via the anterior commissure: progressive and regressive strategies.

ABSTRACT: The anterior commissure (AC) is a phylogenetically conserved inter-hemispheric connection found among vertebrates with bilateral symmetry. The AC connects predominantly olfactory areas but many aspects of its development and structure are unknown. To fill this gap, we investigated the embryonic and postnatal development of the AC by tracing axons with DiI and the piggyback transposon multicolor system. With this strategy, we show that axon growth during establishment of the AC follows a strictly regulated timeline of events that include waiting periods ("regressive strategies") as well as periods of active axon outgrowth ("progressive strategies"). We also provide evidence that these processes may be regulated in the midline via overexpression of chondroitin sulfate proteoglycans. Additionally, we demonstrate that the ipsi- and contralateral innervation of piriform cortex occurs simultaneously. Morphologically, we found that 20% of axons were myelinated by postnatal day (P) 22, in a process that occurred fundamentally around P14. By immunohistochemistry, we described the presence of glial cells and two new subtypes of neurons: one expressing a calretinin (CR)-/MAP2+ phenotype, distributed homogeneously inside the AC; and the other expressing a CR+/MAP2+ phenotype that lies beneath the bed nucleus of the stria terminalis. Our results are consistent with the notion that the AC follows a strictly regulated program during the embryonic and postnatal development similarly to other distal targeting axonal tracts.

SUBMITTER: Martin-Lopez E

PROVIDER: S-EPMC6252112 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Development of piriform cortex interhemispheric connections via the anterior commissure: progressive and regressive strategies.

Martin-Lopez Eduardo E Meller Sarah J SJ Greer Charles A CA

Brain structure & function 20180824 9

The anterior commissure (AC) is a phylogenetically conserved inter-hemispheric connection found among vertebrates with bilateral symmetry. The AC connects predominantly olfactory areas but many aspects of its development and structure are unknown. To fill this gap, we investigated the embryonic and postnatal development of the AC by tracing axons with DiI and the piggyback transposon multicolor system. With this strategy, we show that axon growth during establishment of the AC follows a strictly ...[more]

PMID: 30141078

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Project description:The anterior piriform cortex (APC) is activated by, and is the brain area most sensitive to, essential (indispensable) amino acid (IAA) deficiency. The APC is required for the rapid (20 min) behavioral rejection of IAA deficient diets and increased foraging, both crucial adaptive functions supporting IAA homeostasis in omnivores. The biochemical mechanisms signaling IAA deficiency in the APC block initiation of translation in protein synthesis via uncharged tRNA and the general amino acid control kinase, general control nonderepressing kinase 2. Yet, how inhibition of protein synthesis activates the APC is unknown. The neuronal K(+) Cl(-) cotransporter, neural potassium chloride co-transporter (KCC2), and GABAA receptors are essential inhibitory elements in the APC with short plasmalemmal half-lives that maintain control in this highly excitable circuitry. After a single IAA deficient meal both proteins were reduced (vs. basal diet controls) in western blots of APC (but not neocortex or cerebellum) and in immunohistochemistry of APC. Furthermore, electrophysiological analyses support loss of inhibitory elements such as the GABAA receptor in this model. As the crucial inhibitory function of the GABAA receptor depends on KCC2 and the Cl(-) transmembrane gradient it establishes, these results suggest that loss of such inhibitory elements contributes to disinhibition of the APC in IAA deficiency. The circuitry of the anterior piriform cortex (APC) is finely balanced between excitatory (glutamate, +) and inhibitory (GABA, -) transmission. GABAA receptors use Cl(-), requiring the neural potassium chloride co-transporter (KCC2). Both are rapidly turning-over proteins, dependent on protein synthesis for repletion. In IAA (indispensable amino acid) deficiency, within 20 min, blockade of protein synthesis prevents restoration of these inhibitors; they are diminished; disinhibition ensues. GCN2 = general control non-derepressing kinase 2, eIF2? = ?-subunit of the eukaryotic initiation factor 2.

Dataset Information

Development of piriform cortex interhemispheric connections via the anterior commissure: progressive and regressive strategies.

Publications

Development of piriform cortex interhemispheric connections via the anterior commissure: progressive and regressive strategies.

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