Abstracts

Rationale: The claustrum, a thin layer of grey matter situated between the external and extreme capsules, is extensively and bidirectionally connected with many brain regions, including the basal ganglia, prefrontal, motor, and sensory cortices (1). Although its anatomical connectivity has been investigated, a definitive functional role for the claustrum remains speculative. Recent findings suggest a possible and important role of the claustrum in awareness and consciousness (2,3). Here, through cortico-cortico evoked potentials (CCEPs), we studied the effective connectivity of the claustrum to the contralateral claustrum and to CA3 regions of the hippocampi bilaterally. As the CA3 is a key site of seizure generation in the kainate model in rats, studying its connectivity with the claustrum is part of a larger study that aims at assessing the role of the claustrum in the alteration of consciousness that accompanies temporal lobe seizures. Methods: Seven adult male Sprague-Dawley rats were implanted with tripolar electrodes in bilateral claustra and unipolar electrodes in bilateral CA3 regions. Single-pulse bipolar stimulations, 1 ms in pulse-width at 0.1 Hz, were delivered to the claustrum at current intensities of 200, 400, 600, 800, and 1000 A totalling 100 pulses at each intensity. Stimuli were time-locked and the EEG averaged. CCEP amplitudes, latencies, and total duration of responses were analyzed. Results: Four of the seven rats were excluded from the analysis due to inaccurate electrode placement demonstrated histologically at the end of the study. CCEPs were recorded at each stimulation intensity from bilateral hippocampi and contralateral claustrum. Stimulation of the left claustrum elicited CCEPs in the right claustrum with first peak (N1) latencies ranging from 6-10 ms and CCEPs in bilateral hippocampi with latencies ranging from 4-25 ms. The amplitude range of the CCEPs in the right claustrum were between 280-580 V, and those in bilateral hippocampi between 90-380 V (Fig 1). Similarly, stimulation of the right claustrum elicited CCEPs in the left claustrum with peak latencies from 8-11 ms and voltages of 220-640 V, and CCEPs in bilateral hippocampi had N1 latencies from 10-13 ms and voltages of 60-200 V. All analyzed potentials showed second peak (N2) latencies ranging from 45-140 ms with amplitudes ranging from 30-350 V and showed no amplitude difference between claustral-hippocampal and inter-claustral CCEPs. The total durations of all CCEPs ranged between 90-250 ms. Conclusions: Previous research into the connectivity of the claustrum has primarily utilized tract-tracing methods, (4,5) and we are unaware of effective connectivity studies of this structure. Despite the small number of animals included in the final analysis, our results suggest that the claustrum is involved early in seizures of hippocampal origin, thus contributing to their semiological manifestations, which may include alteration of awareness. References: 1. Crick F.C., Koch, C. (2005). Philos Trans R Soc Lond C BIol Sci. 29;1271-1279. 2. Koubeissi, M.Z., Bartolomei, F., Beltagy, A., Picard, F. (2014).Epilepsy Behav. 37;32-35. 3. Chau, A., Salazar, A.M., Krueger, F., Cristofori, I., Grafman, J. (2015).Conscious Cogn. 36;256-264. 4. Smith J.B., Radhakrishnan H., Alloway, K.D. (2012). J Neurosci. 32;1524-12.2012. 5. Milardi D., Bramanti, P., Milazzo, C. et al. (2015). Cereb Cortex. 25;406-414. Funding: This study was made possible by the startup funds from the George Washington University for MZK.