Biomedical subjects

Reinoud Maex

Publications and source records attributed to Reinoud Maex.

6 recordsLinked to original sources

PubMed2006

Dendritic amplification of inhibitory postsynaptic potentials in a model Purkinje cell.

In neurons with large dendritic arbors, the postsynaptic potentials interact in a complex manner with active and passive membrane properties, causing not easily predictable transformations during the propagation from synapse to soma. Previous theoretical and experimental studies in both cerebellar Purkinje cells and neocortical pyramidal neurons have shown that voltage-dependent ion channels change the amplitude and time-course of postsynaptic potentials. We investigated the mechanisms involved in the propagation of inhibitory postsynaptic potentials (IPSPs) along active dendrites in a model of the Purkinje cell. The amplitude and time-course of IPSPs recorded at the soma were dependent on the synaptic distance from the soma, as predicted by passive cable theory. We show that the effect of distance on the amplitude and width of the IPSP was significantly reduced by the dendritic ion channels, whereas the rise time was not affected. Somatic IPSPs evoked by the activation of the most distal synapses were up to six times amplified owing to the presence of voltage-gated channels and the IPSP width became independent of the covered distance. A transient deactivation of the Ca(2+) channels and the Ca(2+)-dependent K(+) channels, triggered by the hyperpolarization following activation of the inhibitory synapse, was found to be responsible for these dynamics. Nevertheless, the position of activated synapses had a marked effect on the Purkinje cell firing pattern, making stellate cells and basket cells most suitable for controlling the firing rate and spike timing, respectively, of their target Purkinje cells.

Animals↗

PubMed2005

Synaptic pathways in neural microcircuits.

The functions performed by different neural microcircuits depend on the anatomical and physiological properties of the various synaptic pathways connecting neurons. Neural microcircuits across various species and brain regions are similar in terms of their repertoire of neurotransmitters, their synaptic kinetics, their short-term and long-term plasticity, and the target-specificity of their synaptic connections. However, microcircuits can be fundamentally different in terms of the precise recurrent design used to achieve a specific functionality. In this review, which is part of the TINS Microcircuits Special Feature, we compare the connectivity designs in spinal, hippocampal, neocortical and cerebellar microcircuits, and discuss the different computational challenges that each microcircuit faces.

Animals↗

PubMed2005

Oscillations in the cerebellar cortex: a prediction of their frequency bands.

Local recurrent connections endow the cerebellar cortex with an intrinsic dynamics. We performed computer simulations to predict the frequency bands of the oscillations that will most likely emerge. Feedback inhibition from the Golgi to the granule cells induced 10-50 Hz oscillations, the period at resonance being approximately equal to four times the maximum conduction delay generated along the parallel-fiber connections from granule to Golgi cells. In the molecular layer, the interneurons tended to induce fast oscillations (100-250 Hz), having a period equal to about four times the delay over their reciprocal synaptic connections. Finally, although the presence of lateral inhibition among the Purkinje cells has not been firmly established, reciprocal Purkinje-cell synapses are predicted to transform the cerebellar cortex into a potential temporal integrator.

Animals↗

PubMed2005

The effect of NMDA receptors on gain modulation.

The ability of individual neurons to modulate the gain of their input-output function is important for information processing in the brain. In a recent study, shunting inhibition was found to modulate the gain of cerebellar granule cells subjected to simulated currents through AMPA receptor synapses. Here we investigate the effect on gain modulation resulting from adding the currents mediated by NMDA receptors to a compartmental model of the granule cell. With only AMPA receptors, the changes in gain induced by shunting inhibition decreased gradually with the average firing rate of the afferent mossy fibers. With NMDA receptors present, this decrease was more rapid, therefore narrowing the bandwidth of mossy fiber firing rates available for gain modulation. The deterioration of gain modulation was accompanied by a reduced variability of the input current and saturation of NMDA receptors. However, when the output of the granule cell was plotted as a function of the average input current instead of the input firing frequency, both models showed very similar response curves and comparable gain modulation. We conclude that NMDA receptors do not directly impair gain control by shunting inhibition, but the effective bandwidth decreases as a consequence of the increased total charge transfer.

Animals↗

PubMed2004

Inactivation of calcium-binding protein genes induces 160 Hz oscillations in the cerebellar cortex of alert mice.

Oscillations in neuronal populations may either be imposed by intrinsically oscillating pacemakers neurons or emerge from specific attributes of a distributed network of connected neurons. Calretinin and calbindin are two calcium-binding proteins involved in the shaping of intraneuronal Ca2+ fluxes. However, although their physiological function has been studied extensively at the level of a single neuron, little is known about their role at the network level. Here we found that null mutations of genes encoding calretinin or calbindin induce 160 Hz local field potential oscillations in the cerebellar cortex of alert mice. These oscillations reached maximum amplitude just beneath the Purkinje cell bodies and are reinforced in the cerebellum of mice deficient in both calretinin and calbindin. Purkinje cells fired simple spikes phase locked to the oscillations and synchronized along the parallel fiber axis. The oscillations reversibly disappeared when gap junctions or either GABA(A) or NMDA receptors were blocked. Cutaneous stimulation of the whisker region transiently suppressed the oscillations. However, the intrinsic somatic excitability of Purkinje cells recorded in slice preparation was not significantly altered in mutant mice. Functionally, these results suggest that 160 Hz oscillation emerges from a network mechanism combining synchronization of Purkinje cell assemblies through parallel fiber excitation and the network of coupled interneurons of the molecular layer. These findings demonstrate that subtle genetically induced modifications of Ca2+ homeostasis in specific neuron types can alter the observed dynamics of the global network.

Action Potentials↗

PubMed2003

Resonant synchronization in heterogeneous networks of inhibitory neurons.

Brain rhythms arise through the synchronization of neurons and their entrainment in a regular firing pattern. In this process, networks of reciprocally connected inhibitory neurons are often involved, but what mechanism determines the oscillation frequency is not completely understood. Analytical studies predict that the emerging frequency band is primarily constrained by the decay rate of the unitary IPSC. We observed a new phenomenon of resonant synchronization in computer-simulated networks of inhibitory neurons in which the synaptic current has a delayed onset, reflecting finite spike propagation and synaptic transmission times. At the resonant level of network excitation, all neurons fire synchronously and rhythmically with a period approximately four times the mean delay of the onset of the inhibitory synaptic current. The amplitude and decay time constant of the synaptic current have relatively minor effects on the emerging frequency band. By varying the axonal delay of the inhibitory connections, networks with a realistic synaptic kinetics can be tuned to frequencies from 40 to >200 Hz. This resonance phenomenon arises in heterogeneous networks with, on average, as few as five connections per neuron. We conclude that the delay of the synaptic current is the primary parameter controlling the oscillation frequency of inhibitory networks and propose that delay-induced synchronization is a mechanism for fast brain rhythms that depend on intact inhibitory synaptic transmission.

Action Potentials↗