RESUMEN
Changes in neuronal activity are accompanied by the release of vasoactive mediators that cause microscopic dilation and constriction of the cerebral microvasculature and are manifested in macroscopic blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signals. We used two-photon microscopy to measure the diameters of single arterioles and capillaries at different depths within the rat primary somatosensory cortex. These measurements were compared with cortical depth-resolved fMRI signal changes. Our microscopic results demonstrate a spatial gradient of dilation onset and peak times consistent with "upstream" propagation of vasodilation toward the cortical surface along the diving arterioles and "downstream" propagation into local capillary beds. The observed BOLD response exhibited the fastest onset in deep layers, and the "initial dip" was most pronounced in layer I. The present results indicate that both the onset of the BOLD response and the initial dip depend on cortical depth and can be explained, at least in part, by the spatial gradient of delays in microvascular dilation, the fastest response being in the deep layers and the most delayed response in the capillary bed of layer I.
Asunto(s)
Oxígeno/sangre , Corteza Somatosensorial/irrigación sanguínea , Animales , Arteriolas/anatomía & histología , Arteriolas/fisiología , Capilares/anatomía & histología , Capilares/fisiología , Circulación Cerebrovascular/fisiología , Hemodinámica/fisiología , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Microcirculación/fisiología , Microscopía de Fluorescencia por Excitación Multifotónica , Ratas , Ratas Sprague-Dawley , Vasodilatación/fisiologíaRESUMEN
The present study addresses the relationship between blood flow and glucose consumption in rat primary somatosensory cortex (SI) in vivo. We examined bilateral neuronal and hemodynamic changes and 2-deoxyglucose (2DG) uptake, as measured by autoradiography, in response to unilateral forepaw stimulation. In contrast to the contralateral forepaw area, where neuronal activity, blood oxygenation/flow and 2DG uptake increased in unison, we observed, in the ipsilateral SI, a blood oxygenation/flow decrease and arteriolar vasoconstriction in the presence of increased 2DG uptake. Laminar electrophysiological recordings revealed an increase in ipsilateral spiking consistent with the observed increase in 2DG uptake. The vasoconstriction and the decrease in blood flow in the presence of an increase in 2DG uptake in the ipsilateral SI contradict the prominent metabolic hypothesis regarding the regulation of cerebral blood flow, which postulates that the state of neuroglial energy consumption determines the regional blood flow through the production of vasoactive metabolites. We propose that other factors, such as neuronal (and glial) release of messenger molecules, might play a dominant role in the regulation of blood flow in vivo in response to a physiological stimulus.
Asunto(s)
Circulación Cerebrovascular/fisiología , Desoxiglucosa/metabolismo , Potenciales Evocados Somatosensoriales/fisiología , Lateralidad Funcional/fisiología , Corteza Somatosensorial/metabolismo , Animales , Autorradiografía/métodos , Mapeo Encefálico , Radioisótopos de Carbono/metabolismo , Hemodinámica , Hemoglobinas/metabolismo , Oxihemoglobinas/metabolismo , Ratas , Ratas Sprague-Dawley , Corteza Somatosensorial/irrigación sanguínea , Vasoconstricción/fisiologíaRESUMEN
Synaptic transmission initiates a cascade of signal transduction events that couple neuronal activity to local changes in blood flow and oxygenation. Although a number of vasoactive molecules and specific cell types have been implicated, the transformation of stimulus-induced activation of neuronal circuits to hemodynamic changes is still unclear. We use somatosensory stimulation and a suite of in vivo imaging tools to study neurovascular coupling in rat primary somatosensory cortex. Our stimulus evoked a central region of net neuronal depolarization surrounded by net hyperpolarization. Hemodynamic measurements revealed that predominant depolarization corresponded to an increase in oxygenation, whereas predominant hyperpolarization corresponded to a decrease in oxygenation. On the microscopic level of single surface arterioles, the response was composed of a combination of dilatory and constrictive phases. Critically, the relative strength of vasoconstriction covaried with the relative strength of oxygenation decrease and neuronal hyperpolarization. These results suggest that a neuronal inhibition and concurrent arteriolar vasoconstriction correspond to a decrease in blood oxygenation, which would be consistent with a negative blood oxygenation level-dependent functional magnetic resonance imaging signal.
Asunto(s)
Arteriolas/fisiología , Corteza Cerebral/fisiología , Neuronas/fisiología , Oxígeno/sangre , Transmisión Sináptica/fisiología , Vasoconstricción/fisiología , Animales , Volumen Sanguíneo , Mapeo Encefálico , Hemoglobinas/metabolismo , Oxihemoglobinas/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The relationship between measurements of cerebral blood oxygenation and neuronal activity is highly complex and depends on both neurovascular and neurometabolic biological coupling. While measurements of blood oxygenation changes via optical and MRI techniques have been developed to map functional brain activity, there is evidence that the specific characteristics of these signals are sensitive to the underlying vascular physiology and structure of the brain. Since baseline blood flow and oxygen saturation may vary between sessions and across subjects, functional blood oxygenation changes may be a less reliable indicator of brain activity in comparison to blood flow and metabolic changes. In this work, we use a biomechanical model to examine the relationships between neural, vascular, metabolic, and hemodynamic responses to parametric whisker stimulation under both normal and hypercapnic conditions in a rat model. We find that the relationship between neural activity and oxy- and deoxyhemoglobin changes is sensitive to hypercapnia-induced changes in baseline cerebral blood flow. In contrast, the underlying relationships between evoked neural activity, blood flow, and model-estimated oxygen metabolism changes are unchanged by the hypercapnic challenge. We conclude that evoked changes in blood flow and cerebral oxygen metabolism are more closely associated with underlying evoked neuronal responses.