Biomedical subjects

Jakob Wolfart

Publications and source records attributed to Jakob Wolfart.

4 recordsLinked to original sources

PubMed2005

Exploring spike transfer through the thalamus using hybrid artificial-biological neuronal networks.

We use dynamic clamp to construct "hybrid" thalamic circuits by connecting a biological neuron in situ to silicon- or software-generated "neurons" through artificial synapses. The purpose is to explore cellular sensory gating mechanisms that regulate the transfer efficiency of signals during different sleep-wake states. Hybrid technology is applied in vitro to different paradigms such as: (1) simulating interactions between biological thalamocortical neurons, artificial reticular thalamic inhibitory interneurons and a simulated sensory input, (2) grafting an artificial sensory input to a wholly biological thalamic network that generates spontaneous sleep-like oscillations, (3) injecting in thalamocortical neurons a background synaptic bombardment mimicking the activity of corticothalamic inputs. We show that the graded control of the strength of intrathalamic inhibition, combined with the membrane polarization and the fluctuating synaptic noise in thalamocortical neurons, is able to govern functional shifts between different input/output transmission states of the thalamic gate.

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PubMed2005

Synaptic background activity controls spike transfer from thalamus to cortex.

Characterizing the responsiveness of thalamic neurons is crucial to understanding the flow of sensory information. Typically, thalamocortical neurons possess two distinct firing modes. At depolarized membrane potentials, thalamic cells fire single action potentials and faithfully relay synaptic inputs to the cortex. At hyperpolarized potentials, the activation of T-type calcium channels promotes burst firing, and the transfer is less accurate. Our results suggest that this duality no longer holds if synaptic background activity is taken into account. By injecting stochastic conductances into guinea-pig thalamocortical neurons in slices, we show that the transfer function of these neurons is strongly influenced by conductance noise. The combination of synaptic noise with intrinsic properties gives a global responsiveness that is more linear, mixing single-spike and burst responses at all membrane potentials. Because in thalamic neurons, background synaptic input originates mainly from cortex, these results support a determinant role of corticothalamic feedback during sensory information processing.

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PubMed2004

Rescue of mesencephalic dopaminergic neurons in culture by low-level stimulation of voltage-gated sodium channels.

We used a model system in which dopaminergic (DA) neurons from embryonic rat mesencephalon undergo spontaneous and selective degeneration as they develop in culture. Here, we show that DA cell loss can be prevented efficiently by low concentrations of the Na+ channel agonist veratridine. The survival promoting effect of veratridine was reproduced by, but independent of, glial cell line-derived neurotrophic factor. Neuroprotection by veratridine was exquisitely specific to DA neurons, short-lived after withdrawal, and abolished by tetrodotoxin, indicating that activation of voltage-gated Na+ channels was crucially involved. Calcium measurements showed that veratridine-induced Na+ influx was necessary to maintain intracellular Ca2+ within a neuroprotective range through the stimulation of low-voltage activated T-type calcium channels, a mechanism that was distinct from that elicited by high K+-evoked depolarization. Interestingly, increasing neuronal excitability by treatment with apamin, an inhibitor of Ca2+-activated K+ channels, or with ouabain, a blocker of the Na+/K+-ATPase pump, was also neuroprotective by a mechanism involving T-type calcium channel activation. These results support the idea that mesencephalic DA neurons depend primarily on excitatory input for their survival during development.

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PubMed2002

Selective coupling of T-type calcium channels to SK potassium channels prevents intrinsic bursting in dopaminergic midbrain neurons.

Dopaminergic midbrain (DA) neurons display two principal activity patterns in vivo, single-spike and burst firing, the latter coding for reward-related events. We have shown recently that the small-conductance calcium-activated potassium channel SK3 controls pacemaker frequency and precision in DA neurons of the substantia nigra (SN), and previous studies have implicated SK channels in the transition to burst firing. To identify the upstream calcium sources for SK channel activation in DA SN neurons, we studied the sensitivity of SK channel-mediated afterhyperpolarization (AHP) currents to inhibitors of different types of voltage-gated calcium channels in perforated patch-clamp recordings. Cobalt-sensitive AHP currents were not affected by L-type and P/Q-type calcium channel inhibitors and were reduced slightly (26%) by the N-type channel inhibitor omega-conotoxin-GVIA. In contrast, AHP currents were blocked substantially (85-94%) by micromolar concentrations of nickel (IC50, 33.75 microm) and mibefradil (IC50, 4.83 microm), indistinguishable from the nickel and mibefradil sensitivities of T-type calcium currents (IC50 values, 33.86 and 4.59 microm, respectively). These results indicate that SK channels are activated selectively via T-type calcium channels in DA SN neurons. Consequently, SK currents displayed use-dependent inactivation with similar time constants when compared with those of T-type calcium currents and generated a transient rebound inhibition. Both SK and T-type channels were essential for the stability of spontaneous pacemaker activity, and, in some DA SN neurons, T-type channel inhibition was sufficient to induce intrinsic burst firing. The functional coupling of SK to T-type channels has important implications for the temporal integration of synaptic input and might help to understand how DA neurons switch between pacemaker and burst-firing modes in vivo.

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