Search bioRxiv⌕ Search

Biology subjects

Lind, B. L.

Publications and source records attributed to Lind, B. L..

2 recordsLinked to original sources

Astrocytic Ca2+ signals partake in inhibitory neurovascular coupling in a brain state-dependent manner.

Neurovascular coupling (NVC) modulates cerebral blood flow to match increased metabolic demand during neuronal excitation. Activation of inhibitory interneurons also increase blood flow, but the basis for this inhibitory NVC is unclear. We performed two-photon microscopy in awake mice to examine the correlation between astrocytic Ca2+ and NVC, evoked by activity in either all (VGATIN) or parvalbumin-positive GABAergic interneurons (PVIN). Optogenetic stimulation of VGATIN and PVIN in the somatosensory cortex triggered astrocytic Ca2+ increases that were abolished by anaesthesia. PVIN evoked astrocytic Ca2+ responses with a short latency that preceded NVC, whereas VGATIN evoked Ca2+ increases that were delayed relative to the NVC response. The early onset in PVIN evoked Ca2+ increases dependent on noradrenaline release from locus coeruleus, which also affected inhibitory NVC. Therefore, NVC mechanisms should be studied in awake mice and, though the relationship between interneuron activity and astrocytic Ca2+ is complex, we found a correlation between astrocyte activity and NVC in PVIN.

neuroscience↗

Impaired dynamics of brain precapillary sphincters and first order capillaries explains reduced neurovascular functions in aging

The microvascular inflow tract (MIT), comprising the penetrating arterioles, precapillary sphincters, and first order capillaries, is the bottleneck for brain blood flow and energy supply. However, the exact structural and functional alterations of the MIT during aging remain elusive. In vivo 4-dimensional two-photon imaging showed an age-dependent decrease in vaso-responsivity, with reduced sensitivity of the MIT to pinacidil and papaverine, vasoconstrictor endothelin-1, and nitric oxide synthase inhibitor L-NAME. This was accompanied by an age-dependent decrease in capillary density close to the arterioles and loss of pericyte processes, though the number of pericyte somas and pericyte SMA density were preserved. The age-related reduction in vascular reactivity was most pronounced at precapillary sphincters, highlighting their crucial role in capillary blood flow regulation. Mathematical modeling revealed dysregulated but preserved pressure and flow in aged mice during vasoconstriction. Preventing reduced responsivity of the MIT may ameliorate the blood flow decrease associated with aging-related brain frailty.

neuroscience↗