Oscillation Regularity in Noise-Driven Excitable Systems with Multi-Time-Scale Adaptation

We investigate oscillation regularity of a noise-driven system modeled with a slow after-hyperpolarizing adaptation current (AHP) composed of multiple-exponential relaxation time scales. Sufficiently separated slow and fast AHP time scales (biphasic decay) cause a peak in oscillation irregularity for intermediate input currents I, with relatively regular oscillations for small and large currents. An analytic formulation of the system as a stochastic escape problem establishes that the phenomena is distinct from standard forms of coherence resonance. Our results explain data on the oscillation regularity of the pre-Bötzinger complex, a neural oscillator responsible for inspiratory breathing rhythm generation in mammals

Oscillation Regularity in Noise-Driven Excitable Systems with Multi-Time-Scale Adaptation

We investigate oscillation regularity of a noise-driven system modeled with a slow after-hyperpolarizing adaptation current (AHP) composed of multiple-exponential relaxation time scales. Sufficiently separated slow and fast AHP time scales (biphasic decay) cause a peak in oscillation irregularity for intermediate input currents I, with relatively regular oscillations for small and large currents. An analytic formulation of the system as a stochastic escape problem establishes that the phenomena is distinct from standard forms of coherence resonance. Our results explain data on the oscillation regularity of the pre-Bötzinger complex, a neural oscillator responsible for inspiratory breathing rhythm generation in mammals

Information representation in an oscillating neural field model modulated by working memory signals

We study how stimulus information can be represented in the dynamical signatures of an oscillatory model of neural activity—a model whose activity can be modulated by input akin to signals involved in working memory (WM). We developed a neural field model, tuned near an oscillatory instability, in which the WM-like input can modulate the frequency and amplitude of the oscillation. Our neural field model has a spatial-like domain in which an input that preferentially targets a point—a stimulus feature—on the domain will induce feature-specific activity changes. These feature-specific activity changes affect both the mean rate of spikes and the relative timing of spiking activity to the global field oscillation—the phase of the spiking activity. From these two dynamical signatures, we define both a spike rate code and an oscillatory phase code. We assess the performance of these two codes to discriminate stimulus features using an information-theoretic analysis. We show that global WM input modulations can enhance phase code discrimination while simultaneously reducing rate code discrimination. Moreover, we find that the phase code performance is roughly two orders of magnitude larger than that of the rate code defined for the same model solutions. The results of our model have applications to sensory areas of the brain, to which prefrontal areas send inputs reflecting the content of WM. These WM inputs to sensory areas have been established to induce oscillatory changes similar to our model. Our model results suggest a mechanism by which WM signals may enhance sensory information represented in oscillatory activity beyond the comparatively weak representations based on the mean rate activity

Activation of Caspase-8 in the Alzheimer\u27s Disease Brain

Recent studies support the activation of apoptotic pathways in the Alzheimer\u27s disease (AD) brain. Neurons committed to apoptosis may do so by either activation of a receptor-mediated pathway employing caspase-8 or through an alternative mitochondrial pathway involving oxidative stress. In the present study, the role of caspase-8 in the AD brain was examined by designing a caspase-cleavage site-directed antibody to one of the active fragments of caspase-8. In vitro analysis with this antibody, termed CASP-8p18, demonstrated that it recognized the active 18-kDa fragment of caspase-8 but not the precursor protein. In vivo immunohistochemical analysis using hippocampal tissue sections from AD or aged-matched control brains demonstrated CASP-8p18 immunolabeling of neurons in all AD cases, whereas little staining was observed in controls. These results were confirmed using a commercially available antibody that, like the CASP-8p18 antibody reacts only with the 18-kDa fragment of caspase-8 and not full-length caspase-8. As with CASP-8p18 antibody, the commercial antibody-labeled neurons in all AD cases, while showing a relative paucity of staining in representative control cases. Labeling of CASP-8p18 within tangle-bearing neurons was observed in double-labeling studies with AT8 or PHF-1, both markers for neurofibrillary tangles (NFTs). In addition, using a caspase-cleavage site-directed antibody that recognizes cleavage products of caspase-3 showed colocalization of this antibody with the CASP-8p18 antibody within NFTs. These results suggest a role for caspase-8 and the receptor-mediated apoptotic pathway as a mechanism leading to the activation of caspase-3 within neurons of the AD brain