Neuromodulators Control the Polarity of Spike-Timing-Dependent Synaptic Plasticity

Abstract

Near coincidental pre- and postsynaptic action potentials induce associative long-term potentiation (LTP) or long-term depression (LTD), depending on the order of their timing. Here, we show that in visual cortex the rules of this spike-timing-dependent plasticity are not rigid, but shaped by neuromodulator receptors coupled to adenylyl cyclase (AC) and phospholipase C (PLC) signaling cascades. Activation of the AC and PLC cascades results in phosphorylation of postsynaptic glutamate receptors at sites that serve as specific "tags" for LTP and LTD. As a consequence, the outcome (i.e., whether LTP or LTD) of a given pattern of pre- and postsynaptic firing depends not only on the order of the timing, but also on the relative activation of neuromodulator receptors coupled to AC and PLC. These findings indicate that cholinergic and adrenergic neuromodulation associated with the behavioral state of the animal can control the gating and the polarity of cortical plasticity.

Synapse-Specific Control of Experience-Dependent Plasticity by Presynaptic NMDA Receptors

“…In developing sensory cortices (<P20), this protocol results in timing-dependent potentiation (tLTP) when the EPSP precedes the AP and tLTD when the EPSP follows it (Markram et al, 1997; Sjöström et al, 2001). In agreement with previous studies performed in the absence of neuromodulators or GABA(A) receptor antagonists (Corlew et al, 2007; Guo et al, 2012; Seol et al, 2007), we failed to induce either tLTP or tLTD in P26–P30 normally reared (NR) mice (Figures 1A–1E). This suggests that developmental mechanisms tightly regulate STDP in the visual cortex.…”

“…At L4-L2/3 synapses, tLTD in early development (<P20) requires preNMDARs but in later development requires postsynaptic NMDARs and is gated by GABA(A)-receptor signaling or neuromodulators (Corlew et al, 2007; Guo et al, 2012; Seol et al, 2007). To determine whether GABA(A)-mediated signaling acutely influences tLTD in DR mice, we focally blocked GABA(A)-mediated synaptic transmission by applying 50 μM gabazine (SR95531) near the postsynaptic recording pipette (Figures S1B–S1F).…”

Changes in Phospholipid Composition of Synaptic Membranes in Frontal Lobes of Cerebral Hemispheres in Cats at Various Stages of Hemorrhagic Shock

“…Depletion of phosphatidylinositol in SM is probably induced by adrenergic and cholinergic activation. This state is associated with blood loss and results in the expression of phosphatidylinositol-sensitive phospholipase C [14]. Phosphatidylinositol derivatives (phosphoinositides) play a key role in stimulation of neurotransmission.…”

Functional consequences of pre- and postsynaptic expression of synaptic plasticity

“…The neuromodulators can specifically control forms of STDP that express, for example, postsynaptically [109][110][111], providing a potential link between behaviourally relevant behaviours and expression loci.…”