Membrane potential states gate synaptic consolidation in human neocortical tissue.

Synaptic mechanisms that contribute to human memory consolidation remain largely unexplored. Consolidation critically relies on sleep. During slow wave sleep, neurons exhibit characteristic membrane potential oscillations known as UP and DOWN states.

Parvalbumin interneuron cell-to-network plasticity: mechanisms and therapeutic avenues.

Alzheimer's disease (AD) and schizophrenia (SCZ) represent two major neuropathological conditions with a high disease burden. Despite their distinct etiologies, patients suffering from AD or SCZ share a common burden of disrupted memory functions unattended by current therapies. Recent preclinical analyses highlight cell-type-specific contributions of parvalbumin interneurons (PVIs), particularly the plasticity of their cellular excitability, towards intact neuronal network function (cell-to-network plasticity) and memory performance.

Directed and acyclic synaptic connectivity in the human layer 2-3 cortical microcircuit.

The computational capabilities of neuronal networks are fundamentally constrained by their specific connectivity. Previous studies of cortical connectivity have mostly been carried out in rodents; whether the principles established therein also apply to the evolutionarily expanded human cortex is unclear. We studied network properties within the human temporal cortex using samples obtained from brain surgery.

Estimation of persistent sodium-current density in rat hippocampal mossy fibre boutons: Correction of space-clamp errors.

We used whole-cell patch clamp to estimate the stationary voltage dependence of persistent sodium-current density (i) in rat hippocampal mossy fibre boutons. Cox's method for correcting space-clamp errors was extended to the case of an isopotential compartment with attached neurites. The method was applied to voltage-ramp experiments, in which i is assumed to gate instantaneously.

Gamma oscillation plasticity is mediated via parvalbumin interneurons.

Understanding the plasticity of neuronal networks is an emerging field of (patho-) physiological research, yet the underlying cellular mechanisms remain poorly understood. Gamma oscillations (30 to 80 hertz), a biomarker of cognitive performance, require and potentiate glutamatergic transmission onto parvalbumin-positive interneurons (PVIs), suggesting an interface for cell-to-network plasticity. In ex vivo local field potential recordings, we demonstrate long-term potentiation of hippocampal gamma power.

Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation.

Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized.

Objective: The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr).

Methods: Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for Parkinson's disease (PD).

High-throughput microcircuit analysis of individual human brains through next-generation multineuron patch-clamp.

Comparing neuronal microcircuits across different brain regions, species and individuals can reveal common and divergent principles of network computation. Simultaneous patch-clamp recordings from multiple neurons offer the highest temporal and subthreshold resolution to analyse local synaptic connectivity. However, its establishment is technically complex and the experimental performance is limited by high failure rates, long experimental times and small sample sizes.

Connectivity and Dynamics Underlying Synaptic Control of the Subthalamic Nucleus.

Adaptive motor control critically depends on the interconnected nuclei of the basal ganglia in the CNS. A pivotal element of the basal ganglia is the subthalamic nucleus (STN), which serves as a therapeutic target for deep brain stimulation (DBS) in movement disorders, such as Parkinson's disease. The functional connectivity of the STN at the microcircuit level, however, still requires rigorous investigation.

Spike sorting of synchronous spikes from local neuron ensembles.

Synchronous spike discharge of cortical neurons is thought to be a fingerprint of neuronal cooperativity. Because neighboring neurons are more densely connected to one another than neurons that are located further apart, near-synchronous spike discharge can be expected to be prevalent and it might provide an important basis for cortical computations. Using microelectrodes to record local groups of neurons does not allow for the reliable separation of synchronous spikes from different cells, because available spike sorting algorithms cannot correctly resolve the temporally overlapping waveforms.

Sparse but highly efficient Kv3 outpace BKCa channels in action potential repolarization at hippocampal mossy fiber boutons.

Presynaptic elements of axons, in which action potentials (APs) cause release of neurotransmitter, are sites of high densities and complex interactions of proteins. We report that the presence of K(v)3 channels in addition to K(v)1 at glutamatergic mossy fiber boutons (MFBs) in rat hippocampal slices considerably limits the number of fast, voltage-activated potassium channels necessary to achieve basal presynaptic AP repolarization. The ∼ 10-fold higher repolarization efficacy per K(v)3 channel compared with presynaptic K(v)1 results from a higher steady-state availability at rest, a better recruitment by the presynaptic AP as a result of faster activation kinetics, and a larger single-channel conductance.

Role of microcircuit structure and input integration in hippocampal interneuron recruitment and plasticity.

The proper operation of cortical neuronal networks depends on the temporally precise recruitment of GABAergic inhibitory interneurons. Inhibitory cells receive convergent excitatory inputs from afferent pathways, as well as local collaterals of principal cells, and provide feedforward or feedback inhibition within the circuitry. Accumulating evidence indicates that recruitment of GABAergic cells is highly diverse among interneuron types.

Presynaptic glycine receptors on hippocampal mossy fibers.

Presynaptic glycine receptors (GlyRs) have been implicated in the regulation of glutamatergic synaptic transmission. Here, we characterized presynaptic GlyR-mediated currents by patch-clamp recording from mossy fiber boutons (MFBs) in rat hippocampal slices. In MFBs, focal puff-application of glycine-evoked chloride currents that were blocked by the GlyR antagonist strychnine.

Interactions between short-interval intracortical inhibition and short-latency afferent inhibition in human motor cortex.

Transcranial magnetic stimulation (TMS) allows the testing of various inhibitory processes in human motor cortex. Here we aimed at gaining more insight into the underlying physiology by studying the interactions between short-interval intracortical inhibition (SICI) and short-latency afferent inhibition (SAI). SICI and SAI were examined in a slightly contracting hand muscle of healthy subjects by measuring inhibition of a test motor-evoked potential conditioned by a sub-threshold motor cortical magnetic pulse (S1) or an electrical pulse (P) applied to the ulnar nerve at the wrist, respectively.

Energy-efficient action potentials in hippocampal mossy fibers.

Action potentials in nonmyelinated axons are considered to contribute substantially to activity-dependent brain metabolism. Here we show that fast Na+ current decay and delayed K+ current onset during action potentials in nonmyelinated mossy fibers of the rat hippocampus minimize the overlap of their respective ion fluxes. This results in total Na+ influx and associated energy demand per action potential of only 1.

Analog signalling in mammalian cortical axons.

In the mammalian cortex, the classic view assumes that the output information of a neuron is encoded in rather stereotyped action potentials, which provide an all-or-none or digital way of communication between cell body and axonal boutons. A role for subthreshold signal propagation within cortical axons has largely been ignored. Recent achievements of direct recordings from axonal structures in the hippocampus and neocortex extended the classic view by the observation that subthreshold-graded signals propagate down the axon over distances of up to 1 mm.

GABAergic spill-over transmission onto hippocampal mossy fiber boutons.

Presynaptic ionotropic GABA(A) receptors have been suggested to contribute to the regulation of cortical glutamatergic synaptic transmission. Here, we analyzed presynaptic GABA(A) receptor-mediated currents (34 degrees C) recorded from mossy fiber boutons (MFBs) in rat hippocampal slices. In MFBs from young and adult animals, GABA puff application activated currents that were blocked by GABA(A) receptor antagonists.

Combined analog and action potential coding in hippocampal mossy fibers.

In the mammalian cortex, it is generally assumed that the output information of neurons is encoded in the number and the timing of action potentials. Here, we show, by using direct patchclamp recordings from presynaptic hippocampal mossy fiber boutons, that axons transmit analog signals in addition to action potentials. Excitatory presynaptic potentials result from subthreshold dendritic synaptic inputs, which propagate several hundreds of micrometers along the axon and modulate action potential-evoked transmitter release at the mossy fiber-CA3 synapse.

Cortico-motoneuronal excitation of three hand muscles determined by a novel penta-stimulation technique.

The cortico-motoneuronal system (CMS), i.e. the monosynaptic projection from primary motor cortex to motoneurons in lamina IX of the spinal cord is, among all mammals, best developed in humans.

Estimated magnitude and interactions of cortico-motoneuronal and Ia afferent input to spinal motoneurones of the human hand.

Magnitude and interactions of cortico-motoneuronal (CM) and Ia afferent input to spinal alpha-motoneurones (MNs) of the human hand are largely unknown. This is, however, an important question, which bears on the cortical versus peripheral-segmental 'interest' in controlling alpha-MN excitation. Alpha-MN excitation can be quantified by estimating the amplitude of alpha-MN compound excitatory post-synaptic potentials (cEPSPs) from single motor unit (SMU) recordings, if certain assumptions about the membrane trajectory are made [Exp.