5 research outputs found
Reduction of Pentylenetetrazole-Induced Seizure Activity in Awake Rats by Seizure-Triggered Trigeminal Nerve Stimulation
No full textStimulation of the vagus nerve has become an effective method for desynchronizing the highly coherent neural activity typically associated with epileptic seizures. This technique has been used in several animal models of seizures as well as in humans suffering from epilepsy. However, application of this technique has been limited to unilateral stimulation of the vagus nerve, typically delivered according to a fixed duty cycle, independently of whether ongoing seizure activity is present. Here, we report that stimulation of another cranial nerve, the trigeminal nerve, can also cause cortical and thalamic desynchronization, resulting in a reduction of seizure activity in awake rats. Furthermore, we demonstrate that providing this stimulation only when seizure activity begins results in more effective and safer seizure reduction per second of stimulation than with previous methods. Seizure activity induced by intraperitoneal injection of pentylenetetrazole was recorded from microwire electrodes in the thalamus and cortex of awake rats while the infraorbital branch of the trigeminal nerve was stimulated via a chronically implanted nerve cuff electrode. Continuous unilateral stimulation of the trigeminal nerve reduced electrographic seizure activity by up to 78%, and bilateral trigeminal stimulation was even more effective. Using a device that automatically detects seizure activity in real time on the basis of multichannel field potential signals, we demonstrated that seizure-triggered stimulation was more effective than the stimulation protocol involving a fixed duty cycle, in terms of the percent seizure reduction per second of stimulation. In contrast to vagus nerve stimulation studies, no substantial cardiovascular side effects were observed by unilateral or bilateral stimulation of the trigeminal nerve. These findings suggest that trigeminal nerve stimulation is safe in awake rats and should be evaluated as a therapy for human seizures. Furthermore, the results demonstrate that seizure-triggered trigeminal nerve stimulation is technically feasible and could be further developed, in conjunction with real-time seizure-predicting paradigms, to prevent seizures and reduce exposure to nerve stimulation.</jats:p
Circuit asymmetries underlie functional lateralization in the mouse auditory cortex
No full textInternational audienceThe left hemisphere’s dominance in processing social communication has been known for over a century, but the mechanisms underlying this lateralized cortical function are poorly understood. Here, we compare the structure, function, and development of each auditory cortex (ACx) in the mouse to look for specializations that may underlie lateralization. Using Fos brain volume imaging, we found greater activation in the left ACx in response to vocalizations, while the right ACx responded more to frequency sweeps. In vivo recordings identified hemispheric differences in spectrotemporal selectivity, reinforcing their functional differences. We then compared the synaptic connectivity within each hemisphere and discovered lateralized circuit-motifs that are hearing experience-dependent. Our results suggest a specialist role for the left ACx, focused on facilitating the detection of specific vocalization features, while the right ACx is a generalist with the ability to integrate spectrotemporal features more broadly
Asynchronous development of the mouse auditory cortex is driven by hemispheric identity and sex
No full textLateralized auditory processing is essential for specialized functions such as speech processing, typically dominated by the Left Auditory Cortex (ACx) in humans. Hemispheric specializations also occur in the adult mouse ACx, but their developmental origins are unclear. Our study finds that the Left and Right ACx in mice reach developmental milestones at different ages. Thalamocortical responses and maturation of synaptic dynamics develop earlier in the Right ACx than the Left. We show that this timing offset predicts hemisphere-dependent differences in sensory-driven plasticity. Juvenile tone exposure at specific times results in imbalanced adult tone frequency representations in the Right and Left ACx. Additionally, sex influences the timing of plasticity; female Right ACx plasticity occurs before male Right ACx, and female Left ACx aligns with male Right ACx plasticity. Our findings demonstrate that sex and hemispheric identity drive asynchronous development and contribute to functional differences in sensory cortices
Label free, capillary-scale blood flow mapping in vivo reveals that low-intensity focused ultrasound evokes persistent dilation in cortical microvasculature
No full textNon-invasive, low intensity focused ultrasound is an emerging neuromodulation technique that offers the potential for precision, personalized therapy. An increasing body of research has identified mechanosensitive ion channels that can be modulated by FUS and support acute electrical activity in neurons. However, neuromodulatory effects that persist from hours to days have also been reported. The brain\u27s ability to provide blood flow to electrically active regions involves a multitude of non-neuronal cell types and signaling pathways in the cerebral vasculature; an open question is whether persistent effects can be attributed, at least partly, to vascular mechanisms. Using an in vivo optical approach, we found that microvasculature, and not larger vessels, exhibit significant persistent dilation following sonication without the use of microbubbles. This finding reveals a heretofore unseen aspect of the effects of FUS in vivo and indicates that concurrent changes in neurovascular function may partially underly persistent neuromodulatory effects
High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA
No full textSummary Neurons transmit information to distant brain regions via long-range axonal projections. In the mouse, area-to-area connections have only been systematically mapped using bulk labeling techniques, which obscure the diverse projections of intermingled single neurons. Here we describe MAPseq (Multiplexed Analysis of Projections by Sequencing), a technique that can map the projections of thousands or even millions of single neurons by labeling large sets of neurons with random RNA sequences (“barcodes”). Axons are filled with barcode mRNA, each putative projection area is dissected, and the barcode mRNA is extracted and sequenced. Applying MAPseq to the locus coeruleus (LC), we find that individual LC neurons have preferred cortical targets. By recasting neuroanatomy, which is traditionally viewed as a problem of microscopy, as a problem of sequencing, MAPseq harnesses advances in sequencing technology to permit high-throughput interrogation of brain circuits
