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The P13 potential is the rodent equivalent of the P50 potential, which is an evoked response recorded at the vertex (Vx) 50 ms following an auditory stimulus in humans. Both the P13 and P50 potentials are only present during waking and rapid eye movement (REM) sleep, and are considered to be measures of level of arousal. The source of the P13 and P50 potentials appears to be the pedunculopontine nucleus (PPN), a brainstem nucleus with indirect ascending projections to the cortex through the intralaminar thalamus, mediating arousal, and descending inhibitory projections to the caudal pontine reticular formation (CPRF), which mediates the auditory startle response (SR). We tested the hypothesis that intracranial microinjection (ICM) of glutamate (GLU) or GLU receptor agonists will increase the activity of PPN neurons, resulting in an increased P13 potential response, and decreased SR due to inhibitory projections from the PPN to the CPRF, in freely moving animals. Cannulae were inserted into the PPN to inject neuroactive agents, screws were inserted into the Vx in order to record the P13 potential, and electrodes inserted into the dorsal nuchal muscle to record electromyograms and SR amplitude. Our results showed that ICM of GLU into the PPN dose-dependently increased the amplitude of the P13 potential and decreased the amplitude of the SR. Similarly, ICM of N-methyl-d-aspartic acid or kainate into the PPN increased the amplitude of the P13 potential. These findings indicate that glutamatergic input to the PPN plays a role in arousal control in vivo, and changes in glutamatergic input, or excitability of PPN neurons, could be implicated in a number of neuropsychiatric disorders with the common symptoms of hyperarousal and REM sleep dysregulation.

The foundational elements of criminal law, actus reus and mens rca, are vague, imprecise, and indeterminate categories that are based on outdated notions about human behavior. These confused categories affect not only what legally constitutes choice, volition, and intent, but also the defendant's ability to present evidence (since the categories define the evidence that will be admissible), and ultimately, criminal liability. In this Article we explain how neuroscience allows us to reconsider these legal concepts and conceive a more informed view o f human behavior (and therefore criminal liability). The Article explains how distortions in brain function affect the way people perceive reality and how that distortion affects their choices, volition, and intent. It proposes that a more expansive category, encompassing both foundational elements but with a more expanded definition of choice, volition, and intent, would enable judges to permit the mentally ill accused to present scientifically valid expert testimony about how their to present scientifically valid expert testimony about how their illness affects behavior so that the jury will be able to reach an informed decisio [ABSTRACT FROM AUTHOR]

The pedunculopontine nucleus ( PPN) is part of the Reticular Activating System, and active during waking and REM sleep. Previous results showed that all PPN cells plateau at gamma frequencies and intrinsic membrane oscillations in PPN neurons are mediated by high-threshold N- and P/Q-type Ca2+ channels. The present study was designed to determine whether some PPN cells have only N-, only P/Q-, or both N- and P/Q-type Ca2+ channels. We used patch-clamp recordings in PPN cells in slices from anesthetized rat pups in the presence of synaptic receptor blockers ( SB) and Tetrodotoxin ( TTX), and applied ramps to induce intrinsic membrane oscillations. We found that all PPN cell types showed gamma oscillations in the presence of SB+ TTX when using current ramps. In 50% of cells, the N-type Ca2+ channel blocker ω-Conotoxin- GVIA ( ω-CgTx) reduced gamma oscillation amplitude, while subsequent addition of the P/Q-type blocker ω-Agatoxin- IVA ( ω-Aga) blocked the remaining oscillations. Another 20% manifested gamma oscillations that were not significantly affected by the addition of ω-CgTx, however, ω-Aga blocked the remaining oscillations. In 30% of cells, ω-Aga had no effect on gamma oscillations, while ω-CgTx blocked them. These novel results confirm the segregation of populations of PPN cells as a function of the calcium channels expressed, that is, the presence of cells in the PPN that manifest gamma band oscillations through only N-type, only P/Q-type, and both N-type and P/Q-type Ca2+ channels. [ABSTRACT FROM AUTHOR]

The article focuses on the reliability of the functional magnetic resonance imaging (fMRI)-based lie detection to be used as a evidence in the courts neuroimaging for legal purposes other than lie detection which demonstrate lack of intent in criminal cases, or its use in civil litigation.

Epigenetic mechanisms (i.e., histone post-translational modification and DNA methylation) play a role in regulation of gene expression. The pedunculopontine nucleus (PPN), part of the reticular activating system, manifests intrinsic gamma oscillations generated by voltage-dependent, high threshold N- and P/Q-type Ca2+ channels. We studied whether PPN intrinsic gamma oscillations are affected by inhibition of histone deacetylation. We showed that, a) acute in vitro exposure to the histone deacetylation Class I and II inhibitor trichostatin A (TSA, 1 μM) eliminated oscillations in the gamma range, but not lower frequencies, b) pre-incubation with TSA (1 μM, 90-120 min) also decreased gamma oscillations, c) Ca2+ currents (ICa) were reduced by TSA, especially on cells with P/Q-type channels, d) a HDAC Class I inhibitor MS275 (500 nM), and a Class IIb inhibitor Tubastatin A (150-500 nM), failed to affect gamma oscillations, e) MC1568, a HDAC Class IIa inhibitor (1 μM), blocked gamma oscillations, and f) the effects of both TSA and MC1568 were blunted by blockade of CaMKII with KN-93 (1 μM). These results suggest a cell type specific effect on gamma oscillations when histone deacetylation is blocked, suggesting that gamma oscillations through P/Q-type channels modulated by CaMKII may be linked to processes related to gene transcription. [ABSTRACT FROM AUTHOR]

The pedunculopontine nucleus (PPN) is part of the reticular activating system (RAS) in charge of arousal and rapid eye movement sleep. The presence of high-frequency membrane oscillations in the gamma-band range in the PPN has been extensively demonstrated both in vivo and in vitro. Our group previously described histone deacetylation (HDAC) inhibition in vitro induced protein changes in F-actin cytoskeleton and intracellular Ca 2+ concentration regulation proteins in the PPN. Here, we present evidence that supports the presence of a fine balance between HDAC function and calcium calmodulin kinase II-F-actin interactions in the PPN. We modified F-actin polymerization in vitro by using jasplakinolide (1 μM, a promoter of F-actin stabilization), or latrunculin-B (1 μM, an inhibitor of actin polymerization). Our results showed that shifting the balance in either direction significantly reduced PPN gamma oscillation as well as voltage-dependent calcium currents.

The pedunculopontine nucleus (PPN) is part of the Reticular Activating System, and active during waking and REM sleep. Previous results showed that all PPN cells plateau at gamma frequencies and intrinsic membrane oscillations in PPN neurons are mediated by high-threshold N- and P/Q-type Ca(2+) channels. The present study was designed to determine whether some PPN cells have only N-, only P/Q-, or both N- and P/Q-type Ca(2+) channels. We used patch-clamp recordings in PPN cells in slices from anesthetized rat pups in the presence of synaptic receptor blockers (SB) and Tetrodotoxin (TTX), and applied ramps to induce intrinsic membrane oscillations. We found that all PPN cell types showed gamma oscillations in the presence of SB+TTX when using current ramps. In 50% of cells, the N-type Ca(2+) channel blocker ω-Conotoxin-GVIA (ω-CgTx) reduced gamma oscillation amplitude, while subsequent addition of the P/Q-type blocker ω-Agatoxin-IVA (ω-Aga) blocked the remaining oscillations. Another 20% manifested gamma oscillations that were not significantly affected by the addition of ω-CgTx, however, ω-Aga blocked the remaining oscillations. In 30% of cells, ω-Aga had no effect on gamma oscillations, while ω-CgTx blocked them. These novel results confirm the segregation of populations of PPN cells as a function of the calcium channels expressed, that is, the presence of cells in the PPN that manifest gamma band oscillations through only N-type, only P/Q-type, and both N-type and P/Q-type Ca(2+) channels., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

The present study examined how cold pressor stimulation influences electrophysiological correlates of arousal. We measured the P50 auditory evoked response potential in two groups of subjects who immersed their foot in either cold (0-2°C) or room temperature (22-24°C) water for 50 seconds. The P50, which was recorded before and after stimulation, is sleep-state dependent and sensitive to states of arousal in clinical populations. We found a significant reduction in P50 amplitude after exposure to cold, but not room temperature water. In comparison with other studies, these results indicate that cold pressor stimulation in normal subjects may evoke a regulatory process that modulates the P50 amplitude, perhaps to preserve the integrity of sensory perception, even as autonomic and subjective aspects of arousal increase.

We investigated the effects of tinnitus on measures of arousal and attention at various levels of the neuraxis to derive a profile of the pathophysiology of tinnitus. Individuals with tinnitus of at least 6 months' duration (14 male, 15 female) and healthy controls (14 male, 21 female) were tested for arousal and habituation to repetitive stimulation at the brainstem-thalamus level by measuring the P50 potential, a scalp-recorded, auditory-evoked response, using pairs of click stimuli. We used the psychomotor vigilance task, a reaction-time test, to assess attentional processes mediated by thalamocortical functions. We then correlated deficits in arousal and attention, as measured by these tests, with perceived tinnitus severity. Results showed no difference between tinnitus patients and controls in level of arousal or habituation to repetitive sensory stimulation, as measured by the amplitude of the P50 potential and the ability to suppress a second, closely paired stimulus, respectively. However, reaction-time assessments showed that patients with tinnitus have attentional deficits relative to controls (p = .02). We found no significant correlation between sleep disturbance or tinnitus severity and reaction-time testing.