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1.
Sci Adv ; 10(19): eadj9911, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728406

ABSTRACT

During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory interneurons (INs). Whether these inhibitory inputs can shape PNs' projection patterns is, however, unknown. While layer 4 (L4) PNs of the primary somatosensory (S1) cortex are all born as long-range callosal projection neurons (CPNs), most of them acquire local connectivity upon activity-dependent elimination of their interhemispheric axons during postnatal development. Here, we demonstrate that precise developmental regulation of inhibition is key for the retraction of S1L4 PNs' callosal projections. Ablation of somatostatin INs leads to premature inhibition from parvalbumin INs onto S1L4 PNs and prevents them from acquiring their barrel-restricted local connectivity pattern. As a result, adult S1L4 PNs retain interhemispheric projections responding to tactile stimuli, and the mice lose whisker-based texture discrimination. Overall, we show that temporally ordered IN activity during development is key to shaping local ipsilateral S1L4 PNs' projection pattern, which is required for fine somatosensory processing.


Subject(s)
GABAergic Neurons , Interneurons , Somatosensory Cortex , Animals , Interneurons/metabolism , Interneurons/physiology , Interneurons/cytology , GABAergic Neurons/metabolism , GABAergic Neurons/physiology , GABAergic Neurons/cytology , Somatosensory Cortex/physiology , Somatosensory Cortex/metabolism , Somatosensory Cortex/cytology , Mice , Pyramidal Cells/metabolism , Pyramidal Cells/physiology , Parvalbumins/metabolism
2.
Front Neuroanat ; 16: 993421, 2022.
Article in English | MEDLINE | ID: mdl-36157325

ABSTRACT

Hibernation in small mammals is a highly regulated process with periods of torpor involving drops in body temperature and metabolic rate, as well as a general decrease in neural activity, all of which proceed alongside complex brain adaptive changes that appear to protect the brain from extreme hypoxia and low temperatures. All these changes are rapidly reversed, with no apparent brain damage occurring, during the short periods of arousal, interspersed during torpor-characterized by transitory and partial rewarming and activity, including sleep activation, and feeding in some species. The orexins are neuropeptides synthesized in hypothalamic neurons that project to multiple brain regions and are known to participate in the regulation of a variety of processes including feeding behavior, the sleep-wake cycle, and autonomic functions such as brown adipose tissue thermogenesis. Using multiple immunohistochemical techniques and quantitative analysis, we have characterized the orexinergic system in the brain of the Syrian hamster-a facultative hibernator. Our results revealed that orexinergic neurons in this species consisted of a neuronal population restricted to the lateral hypothalamic area, whereas orexinergic fibers distribute throughout the rostrocaudal extent of the brain, particularly innervating catecholaminergic and serotonergic neuronal populations. We characterized the changes of orexinergic cells in the different phases of hibernation based on the intensity of immunostaining for the neuronal activity marker C-Fos and orexin A (OXA). During torpor, we found an increase in C-Fos immunostaining intensity in orexinergic neurons, accompanied by a decrease in OXA immunostaining. These changes were accompanied by a volume reduction and a fragmentation of the Golgi apparatus (GA) as well as a decrease in the colocalization of OXA and the GA marker GM-130. Importantly, during arousal, C-Fos and OXA expression in orexinergic neurons was highest and the structural appearance and the volume of the GA along with the colocalization of OXA/GM-130 reverted to euthermic levels. We discuss the involvement of orexinergic cells in the regulation of mammalian hibernation and, in particular, the possibility that the high activation of orexinergic cells during the arousal stage guides the rewarming as well as the feeding and sleep behaviors characteristic of this phase.

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