Possible contributions of a novel form of synaptic plasticity inAplysiato reward, memory, and their dysfunctions in mammalian brain

Abstract

Recent studies in Aplysia have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate-and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in mammals, where it may contribute to reward, memory, and their dysfunctions in several psychiatric disorders. In Aplysia, spontaneous release is enhanced by activation of presynaptic serotonin receptors, but presynaptic D1 dopamine receptors or nicotinic acetylcholine receptors could play a similar role in mammals. Those receptors enhance spontaneous release of glutamate in hippocampus, entorhinal cortex, prefrontal cortex, ventral tegmental area, and nucleus accumbens. In all of those brain areas, glutamate can activate postsynaptic receptors to elevate Ca 2+ and engage mechanisms of early-phase long-term potentiation (LTP), including AMPA receptor insertion, and of late-phase LTP, including protein synthesis and growth. Thus, presynaptic receptors and spontaneous release may contribute to postsynaptic mechanisms of plasticity in brain regions involved in reward and memory, and could play roles in disorders that affect plasticity in those regions, including addiction, Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD).

A Bayesian context fear learning algorithm/automaton

“…We note that the work of Hasselmo ( 2006 ) provides a precedent for supposing hippocampus to be thrown into different, neuromodulator-controlled modes of operation during encoding and recall and that a variety of neuromodulators are known to affect LTP (e.g., Frey et al, 1989 ; Markram and Segal, 1990 ; Huerta and Lisman, 1995 ; Thomas et al, 1996 . Reviews: Kenney and Gould, 2008 ; Lovinger, 2010 ; Lisman et al, 2011 ; Hawkins, 2013 ).…”

Associative Learning in Invertebrates

“…Dopamine (DA) neurons in the ventral tegmental area (VTA) are thought to mediate reward (Schultz et al 1997;Tsai et al 2009), and are thus analogous to the L29 neurons in Aplysia (except that they are generally activated by appetitive USs). The circuit properties of the VTA DA neurons are similar to those of the L29 neurons in Aplysia, and therefore might account for many of the same behavioral features of learning and reward (Hawkins 2013). In particular, they might explain why the VTA DA neurons increase their firing to the CS and decrease their firing to the US during conditioning, so that they come to fire in expectation of reward (Schultz et al 1997).…”

Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles

“…Synaptic terminals release neurotransmitters either spontaneously or in response to presynaptic action potentials (APs) ( Fatt and Katz, 1952 ). In addition to the well-established role of AP-evoked neurotransmitter release in information transfer and processing, a growing number of studies assign a key role for spontaneous release in synaptic homeostasis and plasticity ( Sutton and Schuman, 2005 ; Kavalali et al, 2011 ; Hawkins, 2013 ). Recent work indicates that these two modes of neurotransmission are largely independent in terms of their presynaptic regulation as well as postsynaptic signaling consequences ( Sara et al, 2005 ; Sutton et al, 2006 , 2007 ; Atasoy et al, 2008 ; Melom et al, 2013 ; Nosyreva et al, 2013 ; Wierda and Sorensen, 2014 ).…”