Brain-wide neural dynamics of poststroke recovery induced by optogenetic stimulation

Abstract

Poststroke optogenetic stimulations can promote functional recovery. However, the circuit mechanisms underlying recovery remain unclear. Elucidating key neural circuits involved in recovery will be invaluable for translating neuromodulation strategies after stroke. Here, we used optogenetic functional magnetic resonance imaging to map brain-wide neural circuit dynamics after stroke in mice treated with and without optogenetic excitatory neuronal stimulations in the ipsilesional primary motor cortex (iM1). We identified key sensorimotor circuits affected by stroke. iM1 stimulation treatment restored activation of the ipsilesional corticothalamic and corticocortical circuits, and the extent of activation was correlated with functional recovery. Furthermore, stimulated mice exhibited higher expression of axonal growth–associated protein 43 in the ipsilesional thalamus and showed increased Synaptophysin+/channelrhodopsin+ presynaptic axonal terminals in the corticothalamic circuit. Selective stimulation of the corticothalamic circuit was sufficient to improve functional recovery. Together, these findings suggest early involvement of corticothalamic circuit as an important mediator of poststroke recovery.

Optogenetic fMRI for Brain-Wide Circuit Analysis of Sensory Processing

“…Primary motor cortex: In human studies, M1 stimulation is generally recommended as a treatment for patients with motor disorders and sensorimotor dysfunction such as Parkinson’s disease, chronic refractory pain, post-stroke recovery, and tinnitus [ 69 ], suggesting that M1 is closely involved throughout the sensorimotor system. ofMRI studies detected brain-wide circuitry driven by M1 stimulation using Thy1-ChR2 mice and AAV-CaMKII-ChR2 [ 10 , 15 , 51 , 52 ]. Optogenetic activation of M1 in Thy1-ChR2 mice showed sequential neural information flow from M1 to the somatosensory pathway (M1→S1→S2/VP) [ 15 ].…”

“…The optogenetic activation of M1 was also used to measure altered brain circuity of M1 after stroke induction by transient middle cerebral artery occlusion (MCAO), resulting in infarction in S1 regions [ 52 ]. In the acute phase (3 days after MCAO), optogenetic activation of M1 failed to increase the fMRI responses even at the stimulated M1 site but rather induced negative fMRI responses.…”

“…Since its first seminal ofMRI study [ 10 ], there has been a rapid growth in ofMRI research. The majority of early ofMRI studies have been limited to the functional mapping of a stimulated region, but improvements in experimental design and acquisition methods have expanded ofMRI applicability in mapping spatiotemporal propagation and processing along with how disease conditions affect brain circuitry as seen in seizures [ 109 , 110 ], Alzheimer’s Disease [ 111 ], stroke [ 52 ], and chronic pain [ 20 ]. Future studies can further delineate the frequency-dependent brain responses of deep-brain nuclei and further characterize circuit changes in other diseases.…”

Clozapine-Induced Chemogenetic Neuromodulation Rescues Post-Stroke Deficits After Chronic Capsular Infarct

“…Recently, chemogenetic and optogenetic neuromodulation have revolutionized brain stimulation because these tools allow selective modulation of neural activity and mapping of brain circuits. Cortical stimulation using these new techniques has significant potential to treat brain disorders that require induction of brain plasticity (e.g., stroke) [10][11][12]. Optogenetic stimulation provides on-off control of neurons or neural circuits with millisecond precision; however, this technique requires not only the implantation of optical devices targeting the particular brain area but also the delivery of a considerable level of energy during prolonged stimulation [13].…”

Data, models and transitions in computational neuroscience : bottom-up and top-down approaches

“…Both depend explicitly on ion concentrations. Recent experimental work on poststroke therapy shows that optogenetically stimulation of thalamocortical and corticothalamic axons aids in restoring sensory function [77,367]. The neural mass demonstrates the differential effects of altered thalamocortical projections on healthy rhythmic behavior, while altered corticothalamic projections do not disrupt healthy activity.…”