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1.
Neuron ; 111(11): 1795-1811.e7, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37023755

RESUMO

Neurons in the prefrontal cortex (PFC) can provide top-down regulation of sensory-affective experiences such as pain. Bottom-up modulation of sensory coding in the PFC, however, remains poorly understood. Here, we examined how oxytocin (OT) signaling from the hypothalamus regulates nociceptive coding in the PFC. In vivo time-lapse endoscopic calcium imaging in freely behaving rats showed that OT selectively enhanced population activity in the prelimbic PFC in response to nociceptive inputs. This population response resulted from the reduction of evoked GABAergic inhibition and manifested as elevated functional connectivity involving pain-responsive neurons. Direct inputs from OT-releasing neurons in the paraventricular nucleus (PVN) of the hypothalamus are crucial to maintaining this prefrontal nociceptive response. Activation of the prelimbic PFC by OT or direct optogenetic stimulation of oxytocinergic PVN projections reduced acute and chronic pain. These results suggest that oxytocinergic signaling in the PVN-PFC circuit constitutes a key mechanism to regulate cortical sensory processing.


Assuntos
Dor Crônica , Núcleo Hipotalâmico Paraventricular , Ratos , Animais , Núcleo Hipotalâmico Paraventricular/metabolismo , Ocitocina/metabolismo , Hipotálamo/metabolismo , Córtex Pré-Frontal/metabolismo
2.
Sci Rep ; 11(1): 14359, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257333

RESUMO

Propagation of activity in spatially structured neuronal networks has been observed in awake, anesthetized, and sleeping brains. How these wave patterns emerge and organize across brain structures, and how network connectivity affects spatiotemporal neural activity remains unclear. Here, we develop a computational model of a two-dimensional thalamocortical network, which gives rise to emergent traveling waves similar to those observed experimentally. We illustrate how spontaneous and evoked oscillatory activity in space and time emerge using a closed-loop thalamocortical architecture, sustaining smooth waves in the cortex and staggered waves in the thalamus. We further show that intracortical and thalamocortical network connectivity, cortical excitation/inhibition balance, and thalamocortical or corticothalamic delay can independently or jointly change the spatiotemporal patterns (radial, planar and rotating waves) and characteristics (speed, direction, and frequency) of cortical and thalamic traveling waves. Computer simulations predict that increased thalamic inhibition induces slower cortical frequencies and that enhanced cortical excitation increases traveling wave speed and frequency. Overall, our results provide insight into the genesis and sustainability of thalamocortical spatiotemporal patterns, showing how simple synaptic alterations cause varied spontaneous and evoked wave patterns. Our model and simulations highlight the need for spatially spread neural recordings to uncover critical circuit mechanisms for brain functions.


Assuntos
Córtex Cerebral/fisiologia , Neurônios/metabolismo , Tálamo/fisiologia , Algoritmos , Simulação por Computador , Eletrodos , Humanos , Modelos Neurológicos , Modelos Teóricos , Neurociências/tendências , Oscilometria , Sono , Vigília
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