Analog modulation of spike-evoked transmission in CA3 circuits is determined by axonal Kv1.1 channels in a time-dependent manner

International audienceSynaptic transmission usually depends on action potentials (APs) in an all-or-none (digital) fashion. Recent studies indicate, however , that subthreshold presynaptic depolarization may facilitate spike-evoked transmission, thus creating an analog modulation of spike-evoked synaptic transmission, also called analog–digital (AD) synaptic facilitation. Yet, the underlying mechanisms behind this facilitation remain unclear. We show here that AD facilitation at rat CA3–CA3 synapses is time-dependent and requires long presynaptic depolarization (5–10 s) for its induction. This depolarization-induced AD facilitation (d-ADF) is blocked by the specific Kv1.1 channel blocker dendrotoxin-K. Using fast voltage-imaging of the axon, we show that somatic depolarization used for induction of d-ADF broadened the AP in the axon through inactivation of Kv1.1 channels. Somatic depolarization enhanced spike-evoked calcium signals in presynaptic terminals, but not basal calcium. In conclusion, axonal Kv1.1 channels determine glutamate release in CA3 neurons in a time-dependent manner through the control of the presynaptic spike waveform

Synaptic dynamics contribute to long-term single neuron response fluctuations

Firing rate variability at the single neuron level is characterized by long-memory processes and complex statistics over a wide range of time scales (from milliseconds up to several hours). Here, we focus on the contribution of non-stationary efficacy of the ensemble of synapses-activated in response to a given stimulus-on single neuron response variability. We present and validate a method tailored for controlled and specific long-term activation of a single cortical neuron in vitro via synaptic or antidromic stimulation, enabling a clear separation between two determinants of neuronal response variability: membrane excitability dynamics vs. synaptic dynamics. Applying this method we show that, within the range of physiological activation frequencies, the synaptic ensemble of a given neuron is a key contributor to the neuronal response variability, long-memory processes and complex statistics observed over extended time scales. Synaptic transmission dynamics impact on response variability in stimulation rates that are substantially lower compared to stimulation rates that drive excitability resources to fluctuate. Implications to network embedded neurons are discussed. \ua9 2014 Reinartz, Biro, Gal, Giugliano and Marom

Monoallelic de novo AJAP1 loss-of-function variants disrupt trans-synaptic control of neurotransmitter release.

Adherens junction-associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed significantly decreased presynaptic GBR levels in Ajap1-/- and Ajap1W183C/+ mice. Consequently, these mice exhibited reduced GBR-mediated presynaptic inhibition at excitatory and inhibitory synapses, along with impaired synaptic plasticity. Our study reveals that AJAP1 enables the postsynaptic neuron to regulate the level of presynaptic GBR-mediated inhibition, supporting the clinical relevance of loss-of-function AJAP1 variants

A review of learning in biologically plausible spiking neural networks

Artificial neural networks have been used as a powerful processing tool in various areas such as pattern recognition, control, robotics, and bioinformatics. Their wide applicability has encouraged researchers to improve artificial neural networks by investigating the biological brain. Neurological research has significantly progressed in recent years and continues to reveal new characteristics of biological neurons. New technologies can now capture temporal changes in the internal activity of the brain in more detail and help clarify the relationship between brain activity and the perception of a given stimulus. This new knowledge has led to a new type of artificial neural network, the Spiking Neural Network (SNN), that draws more faithfully on biological properties to provide higher processing abilities. A review of recent developments in learning of spiking neurons is presented in this paper. First the biological background of SNN learning algorithms is reviewed. The important elements of a learning algorithm such as the neuron model, synaptic plasticity, information encoding and SNN topologies are then presented. Then, a critical review of the state-of-the-art learning algorithms for SNNs using single and multiple spikes is presented. Additionally, deep spiking neural networks are reviewed, and challenges and opportunities in the SNN field are discussed

Presynaptic action potential waveform determines cortical synaptic latency

International audienceNon-technical summary Synaptic delay at cortical synapses is determined by the presynaptic release probability. We show here that the duration and amplitude of the presynaptic action potential also determine synaptic latency at neocortical and hippocampal excitatory synapses. Broadening the presynaptic spike with blockers of potassium channels increased latency by 1–2 ms. Decreasing the amplitude of the presynaptic action potential by partly blocking sodium channels reduced synaptic latency by ∼0.5 ms. These changes may contribute to stabilization of synaptic timing during repetitive stimulation. The regulation of synaptic timing by these pharmacological agents could not be attributed to modulation of axonal conduction. Rather, the effects are compatible with modifications of the kinetics of the presynaptic calcium current. We conclude that synaptic latency at cortical neurons is not constant but dynamically regulated by presynaptic action potential waveform. Abstract Synaptic latency at cortical synapses is determined by the presynaptic release probability (P r). Short-and long-term presynaptic plasticity is associated with modulation of synaptic delay. We show here that the duration and amplitude of the presynaptic action potential also determine synaptic latency at neocortical and hippocampal excitatory synapses. Blockade of voltage-gated potassium (Kv) channels with 4-aminopyridine or dendrotoxin-I, but not tetraethylammonium, induced a 1–2 ms shift in latency at excitatory synaptic connections formed by pairs of neocortical pyramidal neurons. 4-Aminopyridine or dendrotoxin-I, but not tetraethylammonium, increased the duration of the action potential recorded in the axon, suggesting that presynaptic spike duration is controlled by axonal Kv1 potassium channels. Spike width-dependent changes in latency have been identified at the mossy fibre–CA3 cell synapses and contribute to stabilization of synaptic timing during repetitive stimulation. The effects of presynaptic spike amplitude on synaptic latency were also examined. Decreasing the amplitude of the presynaptic action potential with 15–30 nM TTX reduced synaptic latency by ∼0.5 ms. The regulation of synaptic timing by potassium and sodium channel blockers could not be attributed to modulation of axonal conduction. Rather, these effects are compatible with modifications of the kinetics of the presynaptic calcium current. We conclude that synaptic latency at cortical neurons is not constant but dynamically regulated by presynaptic action potential waveform

Enhanced Release Probability without Changes in Synaptic Delay during Analogue–Digital Facilitation

International audienceNeuronal timing with millisecond precision is critical for many brain functions such as sensory perception, learning and memory formation. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). For instance, paired-pulse facilitation or presynaptic long-term potentiation are associated with reductions in the synaptic delay, whereas paired-pulse depression or presynaptic long-term depression are associated with an increased synaptic delay. Parallelly, the AP broadening that results from the inactivation of voltage gated potassium (Kv) channels responsible for the repolarization phase of the AP delays the synaptic response, and the inactivation of sodium (Nav) channels by voltage reduces the synaptic latency. However, whether synaptic delay is modulated during depolarization-induced analogue-digital facilitation (d-ADF), a form of context-dependent synaptic facilitation induced by prolonged depolarization of the presynaptic neuron and mediated by the voltage-inactivation of presynaptic Kv1 channels, remains unclear. We show here that despite Pr being elevated during d-ADF at pyramidal L5-L5 cell synapses, the synaptic delay is surprisingly unchanged. This finding suggests that both Pr and AP-dependent changes in synaptic delay compensate for each other during d-ADF. We conclude that, in contrast to other short-or long-term modulations of presynaptic release, synaptic timing is not affected during d-ADF because of the opposite interaction of Pr and AP-dependent modulations of synaptic delay

Rôle de la probabilité de libération & de la forme du potentiel d'action sur les latences des connexions synaptiques L5-L5 du cortex sensori-moteur de rat

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Release-dependent variations in synaptic latency: a putative code for short- and long-term synaptic dynamics.: Release-dependent latency variation at cortical synapses

International audienceIn the cortex, synaptic latencies display small variations ( approximately 1-2 ms) that are generally considered to be negligible. We show here that the synaptic latency at monosynaptically connected pairs of L5 and CA3 pyramidal neurons is determined by the presynaptic release probability (Pr): synaptic latency being inversely correlated with the amplitude of the postsynaptic current and sensitive to manipulations of Pr. Changes in synaptic latency were also observed when Pr was physiologically regulated in short- and long-term synaptic plasticity. Paired-pulse depression and facilitation were respectively associated with increased and decreased synaptic latencies. Similarly, latencies were prolonged following induction of presynaptic LTD and reduced after LTP induction. We show using the dynamic-clamp technique that the observed covariation in latency and synaptic strength is a synergistic combination that significantly affects postsynaptic spiking. In conclusion, amplitude-related variation in latency represents a putative code for short- and long-term synaptic dynamics in cortical networks