Neuromolecular Imaging and BRODERICK PROBE® nanobiosensors reveal a temporal synchrony in brain rhythms in neural transmission online with movement designs during natural physiology:Temporal asynchrony is imaged online in the same subject during pathology

Abstract

Temporal synchrony, discovered in our laboratory using Live Imaging, Neuromolecular Imaging (NMI), and the BRODERICK PROBE® reveals a distinctive rhythmic regularity between neurotransmitter synaptic release and movement frequency in the natural, physiologic state. Using this innovative nanotechnology of NMI and BRODERICK PROBE® nanobiosensors, a point-by-point temporal synchrony was imaged between the synaptic concentration of serotonin (5-HT) released from structures such as dorsal striatum A9 and ventral striatum A10 terminals, basal nucleus, and ventrolateral nucleus accumbens (vlNAcc) in concert with natural open-field behaviors such as ambulating movement and finer movements of grooming, licking, and chewing. Indeed, 5-HT synaptic concentration increased and decreased in parallel and simultaneously with the rise and fall of open-field behavior frequency. Thus, temporal synchrony occurs when the symphony of physiologic neurochemistry and behavior is uninterrupted by drugs, disease, or injury. In contrast, neurotransmitter release and movement frequency are not in concert when monitoring, for example, psychostimulant-induced behaviors produced by cocaine. After cocaine administration, NMI and BRODERICK PROBE® nanobiosensors revealed temporal asynchrony between endogenous 5-HT release at A10 terminals, basal stem nucleus, somatodendrites, and VTA and both cocaine-induced ambulations and fine movements in freely moving, male Sprague Dawley animals. Temporal asynchrony was also seen during intraoperative, in vivo studies of neurotransmitter release in anterior temporal lobe epilepsy in a human patient. It is likely that time sensitive asynchrony occurred due to the chemical movement of neurotransmitters away from catecholamine and indoleamine neurotransmitters to excitatory neural transmission via the neuropeptide, dynorphin 1-17, that is readily imaged by NMI. NMI recordings with laminar biocompatible carbon-based BRODERICK PROBE® nanobiosensors were taken at a cortical depth of microns to less than 2 mm for 20-30 minute intervals in the epilepsy patient during resection surgery intraoperatively. Importantly, L-tryptophan (L-TP) was imaged online during the operation showing the lack of the ability of the asynchronous brain to produce 5-HT, the hallmark of the synchronous natural state of physiology. Therefore, L-TP and neuropeptides such as excitatory Dynorphins may serve as neurobiomarkers for pharmaco- and/or gene therapy for neurodegenerative processes. In this manner, temporal patterns may be used to create a dynamic data profile in the clinical setting. Although static neurotransmitter levels are currently the standard, these static parameters become more valuable when empirically studied within the context of movement rather than solely focusing on whether a neurotransmitter level has increased or decreased. Not only does this dynamic data provide a more complete portrait of the temporal harmony of physiology, but it may also be used to distinguish the intensity of disease or drug-induced temporal cacophony on specific parts of microneuroanatomy. Therefore, a rhythmic brain, disrupted, may well define brain disease.