Timing Of Synaptic Inputs Research Articles

Modulations of dendritic [formula omitted] spike with weak electric fields in layer 5 pyramidal cells

Weak electric fields (EFs) modulate input/output function of pyramidal cells. Dendritic Ca2+ spike is an important cellular mechanism for coupling synaptic inputs from different cortical layers, which plays a critical role in neuronal computation. This study aims to understand the effects of weak EFs on Ca2+ spikes initiated in the distal dendrites. We use a computational model to simulate dendritic Ca2+ spikes and backpropagating action potentials (APs) in layer 5 pyramidal cells. We apply uniform EFs (less than 20 mV/mm) to the model and examine how they affect the threshold for activation of Ca2+ spikes. We show that the effects of weak field on synaptically evoked Ca2+ spikes depend on the timing of synaptic inputs. When distal inputs coincide with the onset of EFs within a time window of several milliseconds, field-induced depolarization facilitates the initiation of Ca2+ spikes, while field-induced hyperpolarization suppresses dendritic APs. Sustained field-induced depolarization leads to the inactivation of Ca2+ channels and increases the threshold of Ca2+ spike. Sustained field-induced hyperpolarization de-inactivates Ca2+ channels and reduces the threshold of Ca2+ spike. By altering the threshold of backpropagation activated Ca2+ firing, field-induced depolarization increases the degree of coupling between inputs of the soma and distal dendrites, while field-induced hyperpolarization results in a decrease of coupling. The modulatory effects of weak EF are governed by the field direction with respect to the cell. Our study explains a fundamental link between field-induced polarization, dendritic Ca2+ spike, and somato-dendritic coupling. The findings are crucial to interpret how weak EFs achieve specific modulation of cellular activity.

Astrocytes gate Hebbian synaptic plasticity in the striatum.

Astrocytes, via excitatory amino-acid transporter type-2 (EAAT2), are the major sink for released glutamate and contribute to set the strength and timing of synaptic inputs. The conditions required for the emergence of Hebbian plasticity from distributed neural activity remain elusive. Here, we investigate the role of EAAT2 in the expression of a major physiologically relevant form of Hebbian learning, spike timing-dependent plasticity (STDP). We find that a transient blockade of EAAT2 disrupts the temporal contingency required for Hebbian synaptic plasticity. Indeed, STDP is replaced by aberrant non-timing-dependent plasticity occurring for uncorrelated events. Conversely, EAAT2 overexpression impairs the detection of correlated activity and precludes STDP expression. Our findings demonstrate that EAAT2 sets the appropriate glutamate dynamics for the optimal temporal contingency between pre- and postsynaptic activity required for STDP emergence, and highlight the role of astrocytes as gatekeepers for Hebbian synaptic plasticity.

The Time Window for Generation of Dendritic Spikes by Coincidence of Action Potentials and EPSPs is Layer Specific in Somatosensory Cortex

The precise timing of events in the brain has consequences for intracellular processes, synaptic plasticity, integration and network behaviour. Pyramidal neurons, the most widespread excitatory neuron of the neocortex have multiple spike initiation zones, which interact via dendritic and somatic spikes actively propagating in all directions within the dendritic tree. For these neurons, therefore, both the location and timing of synaptic inputs are critical. The time window for which the backpropagating action potential can influence dendritic spike generation has been extensively studied in layer 5 neocortical pyramidal neurons of rat somatosensory cortex. Here, we re-examine this coincidence detection window for pyramidal cell types across the rat somatosensory cortex in layers 2/3, 5 and 6. We find that the time-window for optimal interaction is widest and shifted in layer 5 pyramidal neurons relative to cells in layers 6 and 2/3. Inputs arriving at the same time and locations will therefore differentially affect spike-timing dependent processes in the different classes of pyramidal neurons.

Contribution of astrocytic glutamate and GABA uptake to corticostriatal information processing

The astrocytes, active elements of the tripartite synapse, remove most of the neurotransmitter that spills over the synaptic cleft. Neurotransmitter uptake operated by astrocytes contributes to the strength and timing of synaptic inputs. The striatum, the main input nucleus of basal ganglia, extracts pertinent cortical signals from the background noise and relays cortical information toward basal ganglia output structures. We investigated the role of striatal astrocytic uptake in the shaping of corticostriatal transmission.We performed dual patch-clamp recordings of striatal output neuron (the medium-sized spiny neurons, MSNs)–astrocyte pairs while stimulating the somatosensory cortex. Cortical activity evoked robust synaptically activated transporter-mediated currents (STCs) in 78% of the recorded astrocytes. STCs originated equally from the activities of glutamate transporters and GABA transporters (GATs). Astrocytic STCs reflected here a presynaptic release of neurotransmitters. STCs displayed a large magnitude associated with fast kinetics, denoting an efficient neurotransmitter clearance at the corticostriatal pathway. Inhibition of glutamate transporters type-1 (GLT-1) and GATs decreased the corticostriatal synaptic transmission, through, respectively, desensitization of AMPA receptors and activation of GABAA receptor. STCs displayed a bidirectional short-term plasticity (facilitation for paired-pulse intervals less than 100 ms and depression up to 1 s).We report a genuine facilitation of STCs for high-frequency cortical activity, which could strengthen the detection properties of cortical activity operated by MSNs. MSN EPSCs showed a triphasic short-term plasticity, which was modified by the blockade of GLT-1 or GATs. We show here that neurotransmitter uptake by astrocytes plays a key role in the corticostriatal information processing.

Intracellular Responses of Neurons in the Mouse Inferior Colliculus to Sinusoidal Amplitude-Modulated Tones

Changes in the temporal envelope are important defining features of natural acoustic signals. Many cells in the inferior colliculus (IC) respond preferentially to certain modulation frequencies, but how they accomplish this is not yet clear. We therefore made whole cell patch-clamp recordings in the IC of anesthetized mice while presenting sinusoidal amplitude-modulated (SAM) tones. The relation between the number of evoked spikes and modulation frequency was used to construct rate modulation transfer functions (rMTFs). We observed different types of rate tuning, including band-pass (16%), band-reject (13%), high-pass (6%), and low-pass (6%) tuning. In the high-pass rMTF neurons and some of the low-pass rMTF neurons, the tuning characteristics appeared to be already present in the inputs. In both band-pass and band-reject rMTF neurons, the nonlinear relation between membrane potential and spike probability ensured preferential spiking during only a small part of the modulation period. Band-pass rMTF neurons had rapidly rising excitatory postsynaptic potentials, allowing good phase-locking to brief tones and intermediate modulation frequencies. At low modulation frequencies, adaptation of their spike threshold contributed to the onset response. In contrast, band-reject rMTF neurons responded with small excitatory or inhibitory postsynaptic potentials to brief tones. In these cells, a power law could describe the supralinear relation between average membrane potential and spike rate. Differences in timing of synaptic input and presence or absence of spike adaptation therefore define band-pass and band-reject rate tuning to SAM tones in the mouse IC.

Analysis of synchronization in the response of neurons to noisy periodic synaptic input

The relationship between the timing of synaptic inputs and output spikes of leaky integrate and fire neurons with noisy periodic synaptic input is addressed. The phase transition matrix, relating the input and output spike phases, is calculated. The interspike interval histogram and the period histogram for the neural response to ongoing periodic input are then evaluated by using the leading eigenvector of this phase transition matrix. The dependence of the synchronization index of the neural response upon the number and amplitude of synaptic inputs, the membrane time constant, the average rate of inputs and their frequency of modulation is examined.