Biomedical subjects

Peter Wallén

Publications and source records attributed to Peter Wallén.

7 recordsLinked to original sources

PubMed2006

Effects of flufenamic acid on fictive locomotion, plateau potentials, calcium channels and NMDA receptors in the lamprey spinal cord.

A Ca(2+)-activated, non-selective cation current (I(CAN)) has been suggested to contribute to plateau potentials in lamprey reticulospinal neurons, providing the drive for locomotor initiation. Flufenamic acid (FFA) is commonly used as a blocker of I(CAN). To explore the effects of FFA on spinal locomotor pattern generation, we induced fictive locomotion in the isolated lamprey spinal cord. Bath-applied FFA (100-200microM) caused a marked reduction of amplitude and regularity of the locomotor burst activity. We next analyzed the NMDA-induced membrane potential oscillations in single spinal neurons. The duration of depolarizing plateaus was markedly reduced when applying FFA, suggesting an involvement of I(CAN). However, in experiments with intracellular injection of the Ca(2+) chelator BAPTA, and in the presence of the K(Ca)-channel blocker apamin, no support was found for an involvement of I(CAN). We therefore explored alternative explanations of the effects of FFA. FFA reduced the size of the slow, Ca(2+)-dependent afterhyperpolarization, suggesting an influence on calcium channels. FFA also reduced the NMDA component of reticulospinal EPSPs as well as NMDA-induced depolarizing responses, demonstrating an influence on NMDA receptors. These non-selective effects of FFA can account for its influence on fictive locomotion and on membrane potential oscillations and thus, a specific involvement of the I(CAN) current in the lamprey spinal cord is not supported.

Animals↗

PubMed2005

Cellular signalling properties in microcircuits.

Molecules and cells are the signalling elements in microcircuits. Recent studies have uncovered bewildering diversity in postsynaptic signalling properties in all areas of the vertebrate nervous system. Major effort is now being invested in establishing the specialized signalling properties at the cellular and molecular levels in microcircuits in specific brain regions. This review is part of the TINS Microcircuits Special Feature.

Animals↗

PubMed2004

Scrapie-infected GT1-1 cells show impaired function of voltage-gated N-type calcium channels (Ca(v) 2.2) which is ameliorated by quinacrine treatment.

Prions are transmissible pathogens that cause neurodegenerative diseases, although the mechanisms behind the nervous system dysfunctions are unclear. To study the effects of a prion infection on voltage-gated calcium channels, scrapie-infected gonadotropin-releasing hormone neuronal cells (ScGT1-1) in culture were depolarized by KCl and calcium responses recorded. Lower calcium responses were observed in infected compared to uninfected cells. This effect was still observed when L-type calcium channels were blocked by nimodipine. After inhibition of N-type calcium channels with omega-conotoxin GVIA, there was no difference in calcium responses. The calcium responses after nimodipine treatment became progressively lower during infection, but there was no major loss of the cellular prion protein (PrP(C)) or marked increase in accumulation of the abnormal prion protein (PrP(Sc)) in the cultures. These results indicate that scrapie infection causes a dysfunction of voltage-gated N-type calcium channels, which is exacerbated slowly over time. Quinacrine treatment cleared PrP(Sc) and restored calcium responses in the ScGT1-1 cultures.

Animals↗

PubMed2004

Innate versus learned movements--a false dichotomy?

It is argued that the nervous systems of vertebrates are equipped with a "motor infrastructure," which enables them to perform the full extent of the motor repertoire characteristic of their particular species. In the human, it extends from the networks/circuits underlying locomotion and feeding to sound production in speech and arm-hand-finger coordination. Contrary to current opinion, these diverse motor patterns should be labeled as voluntary, because they can be recruited at will. Moreover, most, if not all, of the motor patterns available at birth are subject to maturation and are modified substantially through learning. We thus argue that the all-too-common distinction between learned and innate movements is based on a fundamental misconception about the neural control of the vertebrate motor system.

Animals↗

PubMed2002

Cellular bases of a vertebrate locomotor system-steering, intersegmental and segmental co-ordination and sensory control.

The isolated brainstem-spinal cord of the lamprey is used as an experimental model in the analysis of the cellular bases of vertebrate locomotor behaviour. In this article we review the neural mechanisms involved in the control of steering, intersegmental co-ordination, as well as the segmental burst generation and the sensory contribution to motor pattern generation. Within these four components of the control system for locomotion, we now have good knowledge of not only the neurones that take part and their synaptic interactions, but also the membrane properties of these neurones, including ion channel subtypes, and their contribution to motor pattern generation.

Animals↗

PubMed2002

Role of apamin-sensitive k(ca) channels for reticulospinal synaptic transmission to motoneuron and for the afterhyperpolarization.

Single motoneurons and pairs of a presynaptic reticulospinal axon and a postsynaptic motoneuron were recorded in the isolated lamprey spinal cord, to investigate the role of calcium-dependent K(+) channels (K(Ca)) during the afterhyperpolarization following the action potential (AHP), and glutamatergic synaptic transmission on the dendritic level. The AHP consists of a fast phase due to transient K(+) channels (fAHP) and a slower phase lasting 100-200 ms (sAHP), being the main determinant of spike frequency regulation. We now present evidence that the sAHP has two components. The larger part, around 80%, is abolished by superfusion of Cd(2+) (blocker of voltage-dependent Ca(2+) channels), by intracellular injection of 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA; fast Ca(2+) chelator), and by apamin (selective toxin for K(Ca) channels of the SK subtype). While 80% of the sAHP is thus due to K(Ca) channels, the remaining 20% is not mediated by Ca(2+), either entering through voltage-dependent Ca(2+) channels or released from intracellular Ca(2+) stores. This Ca(2+)-independent sAHP component has a similar time course as the K(Ca) portion and is not due to a Cl(-) conductance. It may be caused by Na(+)-activated K(+) channels. Glutamatergic excitatory postsynaptic potentials (EPSPs) evoked by single reticulospinal axons give rise to a local Ca(2+) increase in the postsynaptic dendrite, mediated in part by N-methyl-D-aspartate (NMDA) receptors. The Ca(2+) levels remain elevated for several hundred milliseconds and could be expected to activate K(Ca) channels. If so, this activation should cause a local conductance increase in the dendrite that would shunt EPSPs following the first EPSP in a spike train. We have tested this in reticulospinal/motoneuronal pairs, by stimulating the presynaptic axon with spike trains at different frequencies. We compared the first EPSP and the following EPSPs in the control and after blockade with apamin. No difference was observed in EPSP amplitude or shape before and after apamin, either in normal Ringer or in Mg(2+)-free Ringer removing the voltage-dependent block of NMDA receptors. In conclusion, the local Ca(2+) entry during reticulospinal EPSPs does not cause an activation of K(Ca) channels sufficient to affect the efficacy of synaptic transmission. Thus the integration of synaptic signals at the dendritic level in motoneurons appears simpler than would otherwise have been the case.

Action Potentials↗

PubMed2000

Mechanisms of Modulation of a Neural Network.

Neural networks form the basis for the generation and control of various patterns of behavior. Such networks are subjected to modulatory systems that influence their operation and, thereby, the behavior. In the lamprey locomotor network, analysis on the ion channel, synaptic, and cellular levels has given new insights into the organization of such modulatory systems.

Journal Article↗