Spike Timing-Dependent Plasticity with Enhanced Long-Term Depression Leads to an Increase of Statistical Complexity.

Synaptic plasticity is characterized by remodeling of existing synapses caused by strengthening and/or weakening of connections. This is represented by long-term potentiation (LTP) and long-term depression (LTD). The occurrence of a presynaptic spike (or action potential) followed by a temporally nearby postsynaptic spike induces LTP; conversely, if the postsynaptic spike precedes the presynaptic spike, it induces LTD. This form of synaptic plasticity induction depends on the order and timing of the pre- and postsynaptic action potential, and has been termed spike time-dependent plasticity (STDP). After an epileptic seizure, LTD plays an important role as a depressor of synapses, which may lead to their complete disappearance together with that of their neighboring connections until days after the event. Added to the fact that after an epileptic seizure the network seeks to regulate the excess activity through two key mechanisms: depressed connections and neuronal death (eliminating excitatory neurons from the network), LTD becomes of great interest in our study. To investigate this phenomenon, we develop a biologically plausible model that privileges LTD at the triplet level while maintaining the pairwise structure in the STPD and study how network dynamics are affected as neuronal damage increases. We find that the statistical complexity is significantly higher for the network where LTD presented both types of interactions. While in the case where the STPD is defined with purely pairwise interactions an increase is observed as damage becomes higher for both Shannon Entropy and Fisher information.

On the Application of a Diffusive Memristor Compact Model to Neuromorphic Circuits.

Memristive devices have found application in both random access memory and neuromorphic circuits. In particular, it is known that their behavior resembles that of neuronal synapses. However, it is not simple to come by samples of memristors and adjusting their parameters to change their response requires a laborious fabrication process. Moreover, sample to sample variability makes experimentation with memristor-based synapses even harder. The usual alternatives are to either simulate or emulate the memristive systems under study. Both methodologies require the use of accurate modeling equations. In this paper, we present a diffusive compact model of memristive behavior that has already been experimentally validated. Furthermore, we implement an emulation architecture that enables us to freely explore the synapse-like characteristics of memristors. The main advantage of emulation over simulation is that the former allows us to work with real-world circuits. Our results can give some insight into the desirable characteristics of the memristors for neuromorphic applications.

Long-term depression of inhibitory synaptic transmission induced by spike-timing dependent plasticity requires coactivation of endocannabinoid and muscarinic receptors.

The precise timing of pre-postsynaptic activity is vital for the induction of long-term potentiation (LTP) or depression (LTD) at many central synapses. We show in synapses of rat CA1 pyramidal neurons in vitro that spike timing dependent plasticity (STDP) protocols that induce LTP at glutamatergic synapses can evoke LTD of inhibitory postsynaptic currents or STDP-iLTD. The STDP-iLTD requires a postsynaptic Ca(2+) increase, a release of endocannabinoids (eCBs), the activation of type-1 endocananabinoid receptors and presynaptic muscarinic receptors that mediate a decreased probability of GABA release. In contrast, the STDP-iLTD is independent of the activation of nicotinic receptors, GABAB Rs and G protein-coupled postsynaptic receptors at pyramidal neurons. We determine that the downregulation of presynaptic Cyclic adenosine monophosphate/protein Kinase A pathways is essential for the induction of STDP-iLTD. These results suggest a novel mechanism by which the activation of cholinergic neurons and retrograde signaling by eCBs can modulate the efficacy of GABAergic synaptic transmission in ways that may contribute to information processing and storage in the hippocampus.

Long-term potentiation and long-term depression: a clinical perspective

Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.