Alberto Luis Vazquez

Resting-state hemodynamic fluctuations take place over broad temporal scales and are reported to be closely linked to gamma-band neural activity, yet whether specific cell types drive these fluctuations remains unclear. Given the established contribution of parvalbumin (PV) neurons in generating gamma oscillations, they are prime candidates. Using chemogenetic tools in awake PV-Cre mice, we modulated PV interneuron activity and measured effects on neural network activity, EEG, and hemodynamics. Two-photon calcium imaging confirmed their modulation of excitatory neurons as well as local vascular changes. PV chemogenetic suppression reduced EEG gamma power, increased low-frequency EEG activity, and elevated basal CBF. Two-photon imaging under control conditions showed increased basal arterial diameter and significantly greater vascular fluctuation in deeper cortical layers enriched with PV cells, but not in superficial layers. Importantly, PV suppression significantly weakened the correlation between the EEG gamma power and CBF. These findings provide evidence that PV interneuron contribute to spontaneous neurovascular dynamics and to the link between gamma oscillations and resting-state hemodynamic signals, pointing to a significant role in neurovascular changes during non-task-engaged brain states.

Neuronal activity–driven increases in cerebral blood flow (CBF), known as neurovascular coupling (NVC), are crucial for sustaining the metabolic demands of the brain. Our group has found that Tacr1 neurons, a subset of somatostatin neurons expressing the substance P (SP) receptor and neuronal nitric oxide synthase (nNOS), exert a disproportionately large regulation of CBF. Here, we use two-photon imaging to show that Tacr1 neurons regulate CBF through nitric oxide (NO) release and SP-receptor signaling . We identify astrocytic calcium (Ca ²⁺ ) transients as a secondary response to vasodilation. To identify potential sources of SP in somatosensory cortex, viral mapping revealed Tac1 -positive neurons locally, predominantly among parvalbumin (PV) neurons, as well as Tac1 -positive long-range projections from perirhinal cortex. Functional analyses indicate that PV neurons regulate CBF through a Tacr1 neuron dependent pathway. These findings suggest a sequential mechanism whereby Tacr1 neurons respond to SP to release NO, inducing vasodilation and driving astrocytic Ca ²⁺ signaling.

Microstimulation delivers electrical pulses directly into the brain, with one of its promises being to restore lost senses to millions of people. Yet a fundamental challenge remains: how do intracortical microstimulation (ICMS) patterns engage neural circuits to achieve the inception of specific experiences, such as vivid sensory percepts of touch and vision? Here, we define “inception” as the initiation of percepts evoked by microstimulation through the mapping of stimulation to circuit-level activity that results in sensory experiences. This perspective proposes an integrated research framework that combines Reverse Translation, Forward Translation, and computational neuroscience to bridge insights between clinical observations and high-resolution animal studies. Our framework envisions the development and evaluation of ICMS strategies within a cross-species system that narrows the range of plausible underlying neural mechanisms and the set of evoked perceptual outcomes. Reverse Translation uses human perceptual reports about phosphenes, tones, and touch to guide investigations in rodents and non-human primates (NHPs), mapping the cell types and circuits underlying each percept. Forward Translation leverages these biological insights to design refined ICMS protocols for selective circuit engagement. Bidirectional Translation weaves these approaches together through computational neuroscience, ensuring that experimental observations iteratively and continuously refine one another across species and experimental modalities. This integrated strategy aims to transform microstimulation research into a dynamic dialogue between fundamental science and human experience. Harnessing the Bidirectional Translation Framework can accelerate therapies that enhance quality of life for people with sensory or motor impairments, and contribute more broadly to systems neuroscience by uncovering the mechanisms by which causal manipulation changes activity in neurons and networks.

This study used optogenetics and oxygen-sensitive optical imaging to activate targeted neuronal subpopulations and measure changes in CMRO2. We found large changes in CBF and CMRO2 in excitatory neurons and disproportionately larger changes in CBF from inhibitory neurons, which are mostly explained by somatostain-expressing inhibitory neurons.

The editorial introduces the articles in the Neurophotonics Special Issue on Imaging Brain Metabolism and Neuroenergetics.

Neurovascular coupling is the temporal relationship between neuronal activity and regional blood flow changes presumably to meet the high metabolic demands of the brain. Prior fMRI studies have reported excitatory synaptic transmission as more metabolically demanding than neuronal spiking, thus correlating better with cerebral hemodynamics. To investigate this finding with newer optical imaging techniques, we used fluorescent markers for extracellular synaptic glutamate and intracellular neuronal calcium to directly measure relationships between synaptic and spiking activities on local vascular changes in awake mice under evoked and spontaneous conditions. To determine which signal better predicts hemodynamic responses, we used a linear convolution model. Using wide field optical imaging (WFOI), we observed peak fluorescence values of 0.38% and 5.60% in synaptic glutamate and neuronal calcium, respectively, to whisker stimulation, and values of 3.13% and 35.77%, respectively, using two-photon microscopy (2PM). Following whisker stimulation, mean R ² values were 0.64 and 0.79 for synaptic glutamate and neuronal calcium, respectively, with WFOI and 0.67 and 0.56, respectively, with 2PM. From WFOI resting-state, mean R ² values were 0.73 and 0.68 for synaptic glutamate and neuronal calcium, respectively. Altogether, both signals perform similarly in predicting hemodynamic responses, with no significant differences in their prediction efficacy.

Objective. Intracortical microelectrode arrays often fail to deliver reliable signal quality over chronic recordings, and the effect of an implanted recording array on local neural circuits is not completely understood. Approach. In this work we examined the degree of correlation and the spatial dependence of that relationship between widefield calcium imaging and electrophysiology in awake mice from 4 to 44 d post-implantation. Both correlation maps and spike-triggered averaging (STA) are used to characterize the relationship. Main results. We find that calcium imaging and electrophysiological signal are highly correlated in all animals, however, spatial variability in the correlation is affected by inherent correlation in the calcium imaging signal. Some animals exhibit a high degree of apparent neuronal synchrony in the vicinity of the probe at 4 d, while more diversity of response is detected at later time points. Significance. Degree of synchrony appears to be related to the acute injury response to the implanted electrode, with later time points displaying less synchrony. STA may be used to uncover the diverse cortical connections of spiking units.