Journal of Computational Neuroscience

The effects of DBS patterns on basal ganglia activity and thalamic relay : A computational study.

Publication Date: 2012 Jan 13 PMID: 22237601
Authors: Agarwal, R. - Sarma, S. V.
Journal: J Comput Neurosci

Thalamic neurons receive inputs from cortex and their responses are modulated by the basal ganglia (BG). This modulation is necessary to properly relay cortical inputs back to cortex and downstream to the brain stem when movements are planned. In Parkinson's disease (PD), the BG input to thalamus becomes pathological and relay of motor-related cortical inputs is compromised, thereby impairing movements. However, high frequency (HF) deep brain stimulation (DBS) may be used to restore relay reliability, thereby restoring movements in PD patients. Although therapeutic, HF stimulation consumes significant power forcing surgical battery replacements, and may cause adverse side effects. Here, we used a biophysical-based model of the BG-Thalamus motor loop in both healthy and PD conditions to assess whether low frequency stimulation can suppress pathological activity in PD and enable the thalamus to reliably relay movement-related cortical inputs. We administered periodic pulse train DBS waveforms to the sub-thalamic nucleus (STN) with frequencies ranging from 0-140 Hz, and computed statistics that quantified pathological bursting, oscillations, and synchronization in the BG as well as thalamic relay of cortical inputs. We found that none of the frequencies suppressed all pathological activity in BG, though the HF waveforms recovered thalamic reliability. Our rigorous study, however, led us to a novel DBS strategy involving low frequency multi-input phase-shifted DBS, which successfully suppressed pathological symptoms in all BG nuclei and enabled reliable thalamic relay. The neural restoration remained robust to changes in the model parameters characterizing early to late PD stages.

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The faithful copy neuron.

Publication Date: 2012 Jan 11 PMID: 22234837
Authors: Sirovich, L.
Journal: J Comput Neurosci

Theoretical and experimental evidence is presented for the presence in nervous tissue of neurons whose firing rate faithfully follow their input stimulus. Such neurons are shown to deliver their spikes with minimum dissipation per spike. This optimal performance is likely accomplished by use of local circuitry that adjusts conductances to match input currents so that the neuron operates near the threshold for firing. This results in an unusual mechanism for neuronal firing that uses background noise to achieve the desired firing rate. This framework takes place dynamically, and the present deliberations apply under time varying conditions. It is shown that an analytically explicit probability distribution function, which depends on one dimensionless parameter, can account for the interspike interval statistics under general time varying conditions. An innovative analysis based on the unsteady firing rate fits data to the appropriate probability distribution function.

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Does dynamical synchronization among neurons facilitate learning and enhance task performance?

Publication Date: 2012 Jan 8 PMID: 22228383
Authors: Chik, D.
Journal: J Comput Neurosci

Synchronization among groups of neurons is an interesting yet mysterious mechanism in the brain. We propose and demonstrate that the adjustable timing of neural activities can produce profound effect on learning and task implementation. On one hand, learning of more complex patterns becomes possible because of the enhanced capability of classification. On the other hand, implementation of a complex task is aided through active maintenance and control of multiple rules and items. This sheds light on the development of new intelligent system, as well as the cause of impaired learning and task performance in patients.

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Probabilistic modeling of selective stimulation of the human sciatic nerve with a flat interface nerve electrode.

Publication Date: 2012 Jan 6 PMID: 22222951
Authors: Schiefer, M. A. - Tyler, D. J. - Triolo, R. J.
Journal: J Comput Neurosci

Ankle control is critical to both standing balance and efficient walking. The hypothesis presented in this paper is that a Flat Interface Nerve Electrode (FINE) placed around the sciatic nerve with a fixed number of contacts at predetermined locations and without a priori knowledge of the nerve's underlying neuroanatomy can selectively control each ankle motion. Models of the human sciatic nerve surrounded by a FINE of varying size were created and used to calculate the probability of selective activation of axons within any arbitrarily designated, contiguous group of fascicles. Simulations support the hypothesis and suggest that currently available implantable technology cannot selectively recruit each target plantar flexor individually but can restore plantar flexion or dorsiflexion from a site on the sciatic nerve without spillover to antagonists. Successful activation of individual ankle muscles in 90% of the population can be achieved by utilizing bipolar stimulation and/or by using a cuff with at least 20 contacts.

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Spatiotemporal maps of CaMKII in dendritic spines.

Publication Date: 2012 Jan 5 PMID: 22218920
Authors: Khan, S. - Reese, T. S. - Rajpoot, N. - Shabbir, A.
Journal: J Comput Neurosci

The calcium calmodulin dependent kinase (CaMKII) is important for long-term potentiation at dendritic spines. Photo-activatable GFP (PaGFP) - CaMKII fusions were used to map CaMKII movements between and within spines in dissociated hippocampal neurons. Photo-activated PaGFP (GFP*) generated in the shaft spread uniformly, but was retained for about 1 s in spines. The differential localization of GFP*-CaMKII isoforms was visualized with hundred nanometer precision frame to frame using de-noising algorithms. GFP*-CaMKIIalpha localized to the tips of mushroom spines. The spatiotemporal profiles of native and kinase defective GFP*-CaMKIIbeta, differed markedly from GFP*-CaMKIIalpha and mutant GFP*-CaMKIIbeta lacking the association domain. CaMKIIbeta bound to cortical actin in the dendrite and the stable actin network in spine bodies. Glutamate produced a transiently localized GFP*-CaMKIIalpha fraction and a soluble GFP*-CaMKIIbeta fraction in spine bodies. Single molecule simulations of the interplay between diffusion and biochemistry of GFP* species were guided by the spatiotemporal maps and set limits on binding parameters. They highlighted the role of spine morphology in modulating bound CaMKII lifetimes. The long residence times of GFP*-CaMKIIbeta relative to GFP*-CaMKIIalpha followed as consequence of more binding sites on the actin cytoskeleton than the post-synaptic density. These factors combined to retain CaMKII for tens of seconds, sufficient to outlast the calcium transients triggered by glutamate, without invoking complex biochemistry.

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