LTP and LTD: an embarrassment of riches.

A memristor is a two-terminal electronic device whose conductance can be precisely modulated by charge or flux through it. Here we experimentally demonstrate a nanoscale silicon-based memristor device and show that a hybrid system composed of complementary metal−oxide semiconductor neurons and memristor synapses can support important synaptic functions such as spike timing dependent plasticity. Using memristors as synapses in neuromorphic circuits can potentially offer both high connectivity and high density required for efficient computing.

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Nanoscale Memristor Device as Synapse in Neuromorphic Systems

One of the most remarkable aspects of an animal's behavior is the ability to modify that behavior by learning, an ability that reaches its highest form in human beings. For me, learning and memory have proven to be endlessly fascinating mental processes because they address one of the fundamental features of human activity: our ability to acquire new ideas from experience and to retain these ideas over time in memory. Moreover, unlike other mental processes such as thought, language, and consciousness, learning seemed from the outset to be readily accessible to cellular and molecular analysis. I, therefore, have been curious to know: What changes in the brain when we learn? And, once something is learned, how is that information retained in the brain? I have tried to address these questions through a reductionist approach that would allow me to investigate elementary forms of learning and memory at a cellular molecular level-as specific molecular activities within identified nerve cells.

/pdf/the-molecular-biology-of-memory-storage-a-dialogue-between-2cym9imp74.pdf

The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses

Voltage-gated Ca(2+) channels mediate Ca(2+) entry into cells in response to membrane depolarization. Electrophysiological studies reveal different Ca(2+) currents designated L-, N-, P-, Q-, R-, and T-type. The high-voltage-activated Ca(2+) channels that have been characterized biochemically are complexes of a pore-forming alpha1 subunit of approximately 190-250 kDa; a transmembrane, disulfide-linked complex of alpha2 and delta subunits; an intracellular beta subunit; and in some cases a transmembrane gamma subunit. Ten alpha1 subunits, four alpha2delta complexes, four beta subunits, and two gamma subunits are known. The Cav1 family of alpha1 subunits conduct L-type Ca(2+) currents, which initiate muscle contraction, endocrine secretion, and gene transcription, and are regulated primarily by second messenger-activated protein phosphorylation pathways. The Cav2 family of alpha1 subunits conduct N-type, P/Q-type, and R-type Ca(2+) currents, which initiate rapid synaptic transmission and are regulated primarily by direct interaction with G proteins and SNARE proteins and secondarily by protein phosphorylation. The Cav3 family of alpha1 subunits conduct T-type Ca(2+) currents, which are activated and inactivated more rapidly and at more negative membrane potentials than other Ca(2+) current types. The distinct structures and patterns of regulation of these three families of Ca(2+) channels provide a flexible array of Ca(2+) entry pathways in response to changes in membrane potential and a range of possibilities for regulation of Ca(2+) entry by second messenger pathways and interacting proteins.

Structure and regulation of voltage-gated Ca2+ channels.

In the immature brain, GABA (gamma-aminobutyric acid) is excitatory, and GABA-releasing synapses are formed before glutamatergic contacts in a wide range of species and structures. GABA becomes inhibitory by the delayed expression of a chloride exporter, leading to a negative shift in the reversal potential for choride ions. I propose that this mechanism provides a solution to the problem of how to excite developing neurons to promote growth and synapse formation while avoiding the potentially toxic effects of a mismatch between GABA-mediated inhibition and glutamatergic excitation. As key elements of this cascade are activity dependent, the formation of inhibition adds an element of nurture to the construction of cortical networks.

/pdf/excitatory-actions-of-gaba-during-development-the-nature-of-3djowg9wku.pdf

Excitatory actions of gaba during development: the nature of the nurture.

https://www.cell.com/neuron/pdf/S0896-6273(00)80602-9.pdf

Cross Talk between ERK and PKA Is Required for Ca2+ Stimulation of CREB-Dependent Transcription and ERK Nuclear Translocation

https://www.cell.com/cell/pdf/S0092-8674(01)00341-5.pdf

GABA Itself Promotes the Developmental Switch of Neuronal GABAergic Responses from Excitation to Inhibition

Calcium-Stimulated Adenylyl Cyclase Activity Is Critical for Hippocampus-Dependent Long-Term Memory and Late Phase LTP

A p75 NTR and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein

/pdf/a-p75-ntr-and-nogo-receptor-complex-mediates-repulsive-5g96pxz8mn.pdf

Neurotransmitter release at many central synapses is initiated by an influx of calcium ions through P/Q-type calcium channels1,2, which are densely localized in nerve terminals3 Because neurotransmitter release is proportional to the fourth power of calcium concentration4,5, regulation of its entry can profoundly influence neurotransmission N- and P/Q-type calcium channels are inhibited by G proteins6,7, and recent evidence indicates feedback regulation of P/Q-type channels by calcium8 Although calcium-dependent inactivation of L-type channels is well documented9,10,11, little is known about how calcium modulates P/Q-type channels Here we report a calcium-dependent interaction between calmodulin and a novel site in the carboxy-terminal domain of the α1A subunit of P/Q-type channels In the presence of low concentrations of intracellular calcium chelators, calcium influx through P/Q-type channels enhances channel inactivation, increases recovery from inactivation and produces a long-lasting facilitation of the calcium current These effects are prevented by overexpression of a calmodulin-binding inhibitor peptide and by deletion of the calmodulin-binding domain Our results reveal an unexpected association of Ca2+/calmodulin with P/Q-type calcium channels that may contribute to calcium-dependent synaptic plasticity

Scott T. Wong

Papers

Cross Talk between ERK and PKA Is Required for Ca2+ Stimulation of CREB-Dependent Transcription and ERK Nuclear Translocation

GABA Itself Promotes the Developmental Switch of Neuronal GABAergic Responses from Excitation to Inhibition

Calcium-Stimulated Adenylyl Cyclase Activity Is Critical for Hippocampus-Dependent Long-Term Memory and Late Phase LTP

A p75 NTR and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein

Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.