Biology subjects

Ruber, T.

Publications and source records attributed to Ruber, T..

4 recordsLinked to original sources

bioRxiv2020

Sharp-wave ripples in human amygdala and their coordination with hippocampus

Cooperative interactions between the amygdala and hippocampus are widely regarded as critical for overnight emotional processing of waking experiences, but direct support from the human brain for such a dialog is absent. Using intracranial recordings in four pre-surgical epilepsy patients (two male, two female), we discovered ripples within human amygdala during non-rapid eye movement (NREM) sleep. Like hippocampal ripples, amygdala ripples are strongly associated with sharp waves, are linked to sleep spindles, and tend to co-occur with their hippocampal counterparts. Moreover, sharp waves and ripples are temporally linked across the two brain structures, with amygdala ripples occurring during hippocampal sharp waves and vice versa. Combined with further evidence of interregional sharp wave and spindle synchronization, these findings offer a potential physiological substrate for the NREM-sleep-dependent consolidation and regulation of emotional experiences.

neuroscience↗

bioRxiv2019

Potent and lasting seizure suppression by systemic delivery of antagomirs targeting miR-134 timed with blood-brain barrier disruption

RNA therapies such as oligonucleotides (OGNs) offer precision treatments for a variety of neurological diseases, including epilepsy but their deployment is hampered by the blood brain barrier (BBB). Here we used brain imaging and assays of serum proteins and tracer extravasation, to determine that BBB disruption occurring after status epilepticus in mice was sufficient to permit passage of systemically-injected antisense OGNs targeting microRNA-134 (Ant-134) into the brain parenchyma. A single intraperitoneal injection of Ant-134 two hours after status epilepticus in mice resulted in potent suppression of spontaneous recurrent seizures, reaching a 99.5% reduction during recordings at three months. The duration of spontaneous seizures, when they occurred, was also reduced in Ant-134-treated mice. These studies indicate that systemic delivery of Ant-134 reaches the brain and produces disease-modifying effects after systemic injection in mice when timed with BBB disruption and may be a clinically-viable approach for this and other disease-modifying microRNA therapies.

neuroscience↗

bioRxiv2019

Phase-based coordination of hippocampal and neocortical oscillations during human sleep

During sleep, new memories undergo a gradual transfer from the hippocampus (HPC) to the neocortex (NC). Precisely timed neural oscillations interacting within and between these brain structures are thought to mediate this sleep-dependent memory consolidation, but exactly which sleep oscillations instantiate the HPC-NC dialog, and via what mechanisms, remains elusive. Employing invasive electroencephalography in ten neurosurgical patients across a full night of sleep, we identified three broad classes of phase-based HPC-NC communication. First, we observed interregional phase synchrony for non-rapid eye movement (NREM) spindles, N2 and rapid eye movement (REM) theta, and N3 beta activity. Second, and most intriguingly, we found asymmetrical N3 cross-frequency phase-amplitude coupling between HPC SOs and NC activity spanning the delta to high-gamma/ripple bands, but not in the opposite direction. Lastly, N2 theta and NREM spindle synchrony were themselves modulated by HPC SOs. These novel forms of phase-based interregional communication emphasize the role of HPC SOs in the HPC-NC dialog, and may offer a physiological basis for the sleep-dependent reorganization of mnemonic content.

neuroscience↗

bioRxiv2019

Heterogeneous profiles of coupled sleep oscillations in human hippocampus

Cross-frequency coupling of sleep oscillations is thought to mediate memory consolidation. While the hippocampus is deemed central to this process, detailed knowledge of which oscillatory rhythms interact in the sleeping human hippocampus is lacking. Combining intracranial hippocampal and non-invasive electroencephalography from twelve neurosurgical patients, we characterized spectral power and coupling during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Hippocampal coupling was extensive, with the majority of channels expressing spectral interactions. NREM consistently showed delta-ripple coupling, but ripples were also modulated by slow oscillations (SOs) and sleep spindles. SO-delta and SO-theta coupling, as well as interactions between delta/theta and spindle/beta frequencies also occurred. During REM, limited interactions between delta/theta and beta frequencies emerged. Moreover, oscillatory organization differed substantially between i) hippocampus and scalp, ii) sites along the anterior-posterior hippocampal axis, and iii) individuals. Overall, these results extend and refine our understanding of hippocampal sleep oscillations.

neuroscience↗