Rajat S. Shivacharan, Ph.D. is a Postdoctoral Research Fellow in the Department of Neurosurgery sponsored by Dr. Casey H. Halpern (Assistant Professor of Neurosurgery). He received his B.S. in Bioengineering from the University of Maryland in 2013. He went on to earn his Ph.D. in Biomedical Engineering at Case Western Reserve University in May 2019 in the laboratory of Dr. Dominique M. Durand (Director of Neural Engineering Center), studying the role of endogenous electric fields, or ephaptic coupling, in the recruitment of self-propagating, non-synaptic hippocampal waves under pathophysiological conditions. Now, he investigates the role of neuromodulation for neuropsychiatric indications, specifically mechanistic neurophysiology and closed-loop (or responsive) deep brain stimulation (DBS), to improve current neuromodulation therapies for mental disorders with loss of control. Outside of the lab, Rajat likes to cook (or attempt to cook) different types of cuisine, play video games, and enjoys exploring the beautiful Bay Area through biking, hiking, and camping/offroading with his Jeep.
Honors & Awards
Doctoral Excellence Award in Biomedical Engineering, Case Western Reserve University School of Medicine (2019)
1st Place, Senior Capstone – System for Monitoring Endotracheal Tubes with RFID Technology (SMERT), University of Maryland (2013)
Ph.D., Case Western Reserve University, Biomedical Engineering (2019)
B.S., University of Maryland, Bioengineering (2013)
Casey Halpern, Postdoctoral Faculty Sponsor
Self-propagating, non-synaptic epileptiform activity recruits neurons by endogenous electric fields
2019; 317: 119–28
It is well documented that synapses play a significant role in the transmission of information between neurons. However, in the absence of synaptic transmission, neural activity has been observed to continue to propagate. Previous studies have shown that propagation of epileptiform activity takes place in the absence of synaptic transmission and gap junctions and is outside the range of ionic diffusion and axonal conduction. Computer simulations indicate that electric field coupling could be responsible for the propagation of neural activity under pathological conditions such as epilepsy. Electric fields can modulate neuronal membrane voltage, but there is no experimental evidence suggesting that electric field coupling can mediate self-regenerating propagation of neural activity. Here we examine the role of electric field coupling by eliminating all forms of neural communications except electric field coupling with a cut through the neural tissue. We show that 4-AP induced activity generates an electric field capable of recruiting neurons on the distal side of the cut. Experiments also show that applied electric fields with amplitudes similar to endogenous values can induce propagating waves. Finally, we show that canceling the electrical field at a given point can block spontaneous propagation. The results from these in vitro electrophysiology experiments suggest that electric field coupling is a critical mechanism for non-synaptic neural propagation and therefore could contribute to the propagation of epileptic activity in the brain.
View details for DOI 10.1016/j.expneurol.2019.02.005
View details for Web of Science ID 000470803400011
View details for PubMedID 30776338
Slow periodic activity in the longitudinal hippocampal slice can self-propagate non-synaptically by a mechanism consistent with ephaptic coupling
JOURNAL OF PHYSIOLOGY-LONDON
2019; 597 (1): 249–69
Slow periodic activity can propagate with speeds around 0.1 m s-1 and be modulated by weak electric fields. Slow periodic activity in the longitudinal hippocampal slice can propagate without chemical synaptic transmission or gap junctions, but can generate electric fields which in turn activate neighbouring cells. Applying local extracellular electric fields with amplitude in the range of endogenous fields is sufficient to modulate or block the propagation of this activity both in the in silico and in the in vitro models. Results support the hypothesis that endogenous electric fields, previously thought to be too small to trigger neural activity, play a significant role in the self-propagation of slow periodic activity in the hippocampus. Experiments indicate that a neural network can give rise to sustained self-propagating waves by ephaptic coupling, suggesting a novel propagation mechanism for neural activity under normal physiological conditions.Slow oscillations are a standard feature observed in the cortex and the hippocampus during slow wave sleep. Slow oscillations are characterized by low-frequency periodic activity (<1 Hz) and are thought to be related to memory consolidation. These waves are assumed to be a reflection of the underlying neural activity, but it is not known if they can, by themselves, be self-sustained and propagate. Previous studies have shown that slow periodic activity can be reproduced in the in vitro preparation to mimic in vivo slow oscillations. Slow periodic activity can propagate with speeds around 0.1 m s-1 and be modulated by weak electric fields. In the present study, we show that slow periodic activity in the longitudinal hippocampal slice is a self-regenerating wave which can propagate with and without chemical or electrical synaptic transmission at the same speeds. We also show that applying local extracellular electric fields can modulate or even block the propagation of this wave in both in silico and in vitro models. Our results support the notion that ephaptic coupling plays a significant role in the propagation of the slow hippocampal periodic activity. Moreover, these results indicate that a neural network can give rise to sustained self-propagating waves by ephaptic coupling, suggesting a novel propagation mechanism for neural activity under normal physiological conditions.
View details for DOI 10.1113/JP276904
View details for Web of Science ID 000454605100022
View details for PubMedID 30295923
View details for PubMedCentralID PMC6312416
Slow moving neural source in the epileptic hippocampus can mimic progression of human seizures
2018; 8: 1564
Fast and slow neural waves have been observed to propagate in the human brain during seizures. Yet the nature of these waves is difficult to study in a surgical setting. Here, we report an observation of two different traveling waves propagating in the in-vitro epileptic hippocampus at speeds similar to those in the human brain. A fast traveling spike and a slow moving wave were recorded simultaneously with a genetically encoded voltage sensitive fluorescent protein (VSFP Butterfly 1.2) and a high speed camera. The results of this study indicate that the fast traveling spike is NMDA-sensitive but the slow moving wave is not. Image analysis and model simulation demonstrate that the slow moving wave is moving slowly, generating the fast traveling spike and is, therefore, a moving source of the epileptiform activity. This slow moving wave is associated with a propagating neural calcium wave detected with calcium dye (OGB-1) but is independent of NMDA receptors, not related to ATP release, and much faster than those previously recorded potassium waves. Computer modeling suggests that the slow moving wave can propagate by the ephaptic effect like epileptiform activity. These findings provide an alternative explanation for slow propagation seizure wavefronts associated with fast propagating spikes.
View details for DOI 10.1038/s41598-018-19925-7
View details for Web of Science ID 000423154000094
View details for PubMedID 29367722
View details for PubMedCentralID PMC5784157
Propagating Neural Source Revealed by Doppler Shift of Population Spiking Frequency
JOURNAL OF NEUROSCIENCE
2016; 36 (12): 3495–3505
Electrical activity in the brain during normal and abnormal function is associated with propagating waves of various speeds and directions. It is unclear how both fast and slow traveling waves with sometime opposite directions can coexist in the same neural tissue. By recording population spikes simultaneously throughout the unfolded rodent hippocampus with a penetrating microelectrode array, we have shown that fast and slow waves are causally related, so a slowly moving neural source generates fast-propagating waves at ∼0.12 m/s. The source of the fast population spikes is limited in space and moving at ∼0.016 m/s based on both direct and Doppler measurements among 36 different spiking trains among eight different hippocampi. The fact that the source is itself moving can account for the surprising direction reversal of the wave. Therefore, these results indicate that a small neural focus can move and that this phenomenon could explain the apparent wave reflection at tissue edges or multiple foci observed at different locations in neural tissue.The use of novel techniques with an unfolded hippocampus and penetrating microelectrode array to record and analyze neural activity has revealed the existence of a source of neural signals that propagates throughout the hippocampus. The source itself is electrically silent, but its location can be inferred by building isochrone maps of population spikes that the source generates. The movement of the source can also be tracked by observing the Doppler frequency shift of these spikes. These results have general implications for how neural signals are generated and propagated in the hippocampus; moreover, they have important implications for the understanding of seizure generation and foci localization.
View details for DOI 10.1523/JNEUROSCI.3525-15.2016
View details for Web of Science ID 000372747100011
View details for PubMedID 27013678
View details for PubMedCentralID PMC4804007
Can Neural Activity Propagate by Endogenous Electrical Field?
JOURNAL OF NEUROSCIENCE
2015; 35 (48): 15800–15811
It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion. The only explanation left is an electrical field effect. We tested the hypothesis that endogenous electric fields are sufficient to explain the propagation with in silico and in vitro experiments. Simulation results show that field effects alone can indeed mediate propagation across layers of neurons with speeds of 0.12 ± 0.09 m/s with pathological kinetics, and 0.11 ± 0.03 m/s with physiologic kinetics, both generating weak field amplitudes of ∼2-6 mV/mm. Further, the model predicted that propagation speed values are inversely proportional to the cell-to-cell distances, but do not significantly change with extracellular resistivity, membrane capacitance, or membrane resistance. In vitro recordings in mice hippocampi produced similar speeds (0.10 ± 0.03 m/s) and field amplitudes (2.5-5 mV/mm), and by applying a blocking field, the propagation speed was greatly reduced. Finally, osmolarity experiments confirmed the model's prediction that cell-to-cell distance inversely affects propagation speed. Together, these results show that despite their weak amplitude, electric fields can be solely responsible for spike propagation at ∼0.1 m/s. This phenomenon could be important to explain the slow propagation of epileptic activity and other normal propagations at similar speeds.
View details for DOI 10.1523/JNEUROSCI.1045-15.2015
View details for Web of Science ID 000366055500004
View details for PubMedID 26631463
View details for PubMedCentralID PMC4666910
Propagation of Epileptiform Activity Can Be Independent of Synaptic Transmission, Gap Junctions, or Diffusion and Is Consistent with Electrical Field Transmission
JOURNAL OF NEUROSCIENCE
2014; 34 (4): 1409–19
The propagation of activity in neural tissue is generally associated with synaptic transmission, but epileptiform activity in the hippocampus can propagate with or without synaptic transmission at a speed of ∼0.1 m/s. This suggests an underlying common nonsynaptic mechanism for propagation. To study this mechanism, we developed a novel unfolded hippocampus preparation, from CD1 mice of either sex, which preserves the transverse and longitudinal connections and recorded activity with a penetrating microelectrode array. Experiments using synaptic transmission and gap junction blockers indicated that longitudinal propagation is independent of chemical or electrical synaptic transmission. Propagation speeds of 0.1 m/s are not compatible with ionic diffusion or pure axonal conduction. The only other means of communication between neurons is through electric fields. Computer simulations revealed that activity can indeed propagate from cell to cell solely through field effects. These results point to an unexpected propagation mechanism for neural activity in the hippocampus involving endogenous field effect transmission.
View details for DOI 10.1523/JNEUROSCI.3877-13.2014
View details for Web of Science ID 000330360700031
View details for PubMedID 24453330
View details for PubMedCentralID PMC3898297