Learning to Discriminate Through Long-Term Changes of Dynamical Synaptic Transmission

Short-term synaptic plasticity is modulated by long-term synaptic changes. There is, however, no general agreement on the computational role of this interaction. Here, we derive a learning rule for the release probability and the maximal synaptic conductance in a circuit model with combined recurrent and feedforward connections that allows learning to discriminate among natural inputs. Short-term synaptic plasticity thereby provides a nonlinear expansion of the input space of a linear classifier, whereas the random recurrent network serves to decorrelate the expanded input space. Computer simulations reveal that the twofold increase in the number of input dimensions through short-term synaptic plasticity improves the performance of a standard perceptron up to 100%. The distributions of release probabilities and maximal synaptic conductances at the capacity limit strongly depend on the balance between excitation and inhibition. The model also suggests a new computational interpretation of spikes evoked by stimuli outside the classical receptive field. These neuronal activitiesmay reflect decorrelation of the expanded stimulus space by intracortical synaptic connections

Spiking neurons with short-term synaptic plasticity form superior generative networks

Spiking networks that perform probabilistic inference have been proposed both as models of cortical computation and as candidates for solving problems in machine learning. However, the evidence for spike-based computation being in any way superior to non-spiking alternatives remains scarce. We propose that short-term plasticity can provide spiking networks with distinct computational advantages compared to their classical counterparts. In this work, we use networks of leaky integrate-and-fire neurons that are trained to perform both discriminative and generative tasks in their forward and backward information processing paths, respectively. During training, the energy landscape associated with their dynamics becomes highly diverse, with deep attractor basins separated by high barriers. Classical algorithms solve this problem by employing various tempering techniques, which are both computationally demanding and require global state updates. We demonstrate how similar results can be achieved in spiking networks endowed with local short-term synaptic plasticity. Additionally, we discuss how these networks can even outperform tempering-based approaches when the training data is imbalanced. We thereby show how biologically inspired, local, spike-triggered synaptic dynamics based simply on a limited pool of synaptic resources can allow spiking networks to outperform their non-spiking relatives.Comment: corrected typo in abstrac

Molecular mechanisms that stabilize short term synaptic plasticity during presynaptic homeostatic plasticity.

Presynaptic homeostatic plasticity (PHP) compensates for impaired postsynaptic neurotransmitter receptor function through a rapid, persistent adjustment of neurotransmitter release, an effect that can exceed 200%. An unexplained property of PHP is the preservation of short-term plasticity (STP), thereby stabilizing activity-dependent synaptic information transfer. We demonstrate that the dramatic potentiation of presynaptic release during PHP is achieved while simultaneously maintaining a constant ratio of primed to super-primed synaptic vesicles, thereby preserving STP. Mechanistically, genetic, biochemical and electrophysiological evidence argue that a constant ratio of primed to super-primed synaptic vesicles is achieved by the concerted action of three proteins: Unc18, Syntaxin1A and RIM. Our data support a model based on the regulated availability of Unc18 at the presynaptic active zone, a process that is restrained by Syntaxin1A and facilitated by RIM. As such, regulated vesicle priming/super-priming enables PHP to stabilize both synaptic gain and the activity-dependent transfer of information at a synapse

Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity : facilitation through buffer dislocation

Action potential-dependent release of synaptic vesicles and short-term synaptic plasticity are dynamically regulated by the endogenous Ca2+ buffers that shape [Ca2+] profiles within a presynaptic bouton. Calmodulin is one of the most abundant presynaptic proteins and it binds Ca2+ faster than any other characterized endogenous neuronal Ca2+ buffer. Direct effects of calmodulin on fast presynaptic Ca2+ dynamics and vesicular release however have not been studied in detail. Using experimentally constrained three-dimensional diffusion modeling of Ca2+ influx–exocytosis coupling at small excitatory synapses we show that, at physiologically relevant concentrations, Ca2+ buffering by calmodulin plays a dominant role in inhibiting vesicular release and in modulating short-term synaptic plasticity. We also propose a novel and potentially powerful mechanism for short-term facilitation based on Ca2+-dependent dynamic dislocation of calmodulin molecules from the plasma membrane within the active zone

Short-term synaptic plasticity regulates the level of olivocochlear inhibition to auditory hair cells

In the mammalian inner ear, the gain control of auditory inputs is exerted by medial olivocochlear (MOC) neurons that innervate cochlear outer hair cells (OHCs). OHCs mechanically amplify the incoming sound waves by virtue of their electromotile properties while the MOC system reduces the gain of auditory inputs by inhibiting OHC function. How this process is orchestrated at the synaptic level remains unknown. In the present study, MOC firing was evoked by electrical stimulation in an isolated mouse cochlear preparation, while OHCs postsynaptic responses were monitored by whole-cell recordings. These recordings confirmed that electrically evoked IPSCs (eIPSCs) are mediated solely by α9β10 nAChRs functionally coupled to calcium-activated SK2 channels. Synaptic release occurred with low probability when MOC-OHC synapses were stimulated at 1 Hz. However, as the stimulation frequency was raised, the reliability of release increased due to presynaptic facilitation. In addition, the relatively slow decay of eIPSCs gave rise to temporal summation at stimulation frequencies >10 Hz. The combined effect of facilitation and summation resulted in a frequency-dependent increase in the average amplitude of inhibitory currents in OHCs. Thus, we have demonstrated that short-term plasticity is responsible for shaping MOC inhibition and, therefore, encodes the transfer function from efferent firing frequency to the gain of the cochlear amplifier.Fil: Ballestero, Jimena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Zorrilla de San Martín, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Goutman, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Fuchs, Paul A.. The Johns Hopkins University School of Medicine; Estados UnidosFil: Katz, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentin