RESUMO
We review the organizational principles of the cortical vasculature and the underlying patterns of blood flow under normal conditions and in response to occlusion of single vessels. The cortex is sourced by a two-dimensional network of pial arterioles that feeds a three-dimensional network of subsurface microvessels in close proximity to neurons and glia. Blood flow within the surface and subsurface networks is largely insensitive to occlusion of a single vessel within either network. However, the penetrating arterioles that connect the pial network to the subsurface network are bottlenecks to flow; occlusion of even a single penetrating arteriole results in the death of a 500 µm diameter cylinder of cortical tissue despite the potential for collateral flow through microvessels. This pattern of flow is consistent with that calculated from a full reconstruction of the angioarchitecture. Conceptually, collateral flow is insufficient to compensate for the occlusion of a penetrating arteriole because penetrating venules act as shunts of blood that flows through collaterals. Future directions that stem from the analysis of the angioarchitecture concern cellular-level issues, in particular the regulation of blood flow within the subsurface microvascular network, and system-level issues, in particular the role of penetrating arteriole occlusions in human cognitive impairment.
Assuntos
Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular , Microcirculação , Animais , Arteríolas/metabolismo , Arteríolas/patologia , Arteríolas/fisiopatologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Humanos , Neuroglia/metabolismo , Neuroglia/patologia , Neurônios/metabolismo , Neurônios/patologiaRESUMO
Greater loneliness as well as a lack of social connectedness have often been associated with poorer sleep. However, the temporal dynamics and direction of these associations remain unclear. Aim of the current study was to examine bi-directional associations between loneliness/social connectedness and sleep in 48 stress-exposed medical students during their first medical internship, considered a period of heightened stress. We obtained trait-level questionnaire data on loneliness and global sleep completed before and during the internship as well as state-level diary- and wearable-based data on daily changes in social connectedness and sleep collected twice over the period of seven consecutive days, once before and once during the internship. Bi-directional associations among greater loneliness and higher daytime dysfunction on trait-level were identified. In addition, several uni-directional associations between loneliness/social connectedness and sleep were found on trait- and state-level. In sum, findings of this study point at a bi-directional relation among loneliness/social connectedness and sleep, in which variables seem to reciprocally influence each other across longer-term periods as well as on a day-to-day basis.
Assuntos
Solidão , Sono , Solidão/psicologia , Humanos , Masculino , Feminino , Sono/fisiologia , Inquéritos e Questionários , Adulto , Adulto Jovem , Estudantes de Medicina/psicologia , Estresse Psicológico/psicologiaRESUMO
In central mammalian neurons, activation of metabotropic glutamate receptor type1 (mGluR1) evokes a complex synaptic response consisting of IP3 receptor-dependent Ca(2+) release from internal Ca(2+) stores and a slow depolarizing potential involving TRPC3 channels. It is largely unclear how mGluR1 is linked to its downstream effectors. Here, we explored the role of stromal interaction molecule 1 (STIM1) in regulating neuronal Ca(2+) signaling and mGluR1-dependent synaptic transmission. By analyzing mouse cerebellar Purkinje neurons, we demonstrate that STIM1 is an essential regulator of the Ca(2+) level in neuronal endoplasmic reticulum Ca(2+) stores. Both mGluR1-dependent synaptic potentials and IP3 receptor-dependent Ca(2+) signals are strongly attenuated in the absence of STIM1. Furthermore, the Purkinje neuron-specific deletion of Stim1 causes impairments in cerebellar motor behavior. Together, our results demonstrate that in the mammalian nervous system STIM1 is a key regulator of intracellular Ca(2+) signaling, metabotropic glutamate receptor-dependent synaptic transmission, and motor coordination.
Assuntos
Sinalização do Cálcio/fisiologia , Cerebelo/fisiologia , Glicoproteínas de Membrana/fisiologia , Atividade Motora/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Transmissão Sináptica/fisiologia , Animais , Canais de Cálcio , Cerebelo/citologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Neurônios/fisiologia , Técnicas de Cultura de Órgãos , Molécula 1 de Interação EstromalRESUMO
Corticothalamic slow oscillations of neuronal activity determine internal brain states. At least in the cortex, the electrical activity is associated with large neuronal Ca(2+) transients. Here we implemented an optogenetic approach to explore causal features of the generation of slow oscillation-associated Ca(2+) waves in the in vivo mouse brain. We demonstrate that brief optogenetic stimulation (3-20 ms) of a local group of layer 5 cortical neurons is sufficient for the induction of global brain Ca(2+) waves. These Ca(2+) waves are evoked in an all-or-none manner, exhibit refractoriness during repetitive stimulation, and propagate over long distances. By local optogenetic stimulation, we demonstrate that evoked Ca(2+) waves initially invade the cortex, followed by a secondary recruitment of the thalamus. Together, our results establish that synchronous activity in a small cluster of layer 5 cortical neurons can initiate a global neuronal wave of activity suited for long-range corticothalamic integration.