Abstract
Synaptic efficacy changes, long-term potentiation (LTP) and depression (LTD), underlie various forms of learning and memory. Synaptic plasticity is generally assessed under prolonged activation, whereas learning can emerge from few or even a single trial. Here, we investigated the existence of rapid responsiveness of synaptic plasticity in response to a few number of spikes, in neocortex in a synaptic Hebbian learning rule, the spike-timing-dependent plasticity (STDP). We investigated the effect of lowering the number of pairings from 100 to 50, and 10 on STDP expression, using whole-cell recordings from pyramidal cells in rodent somatosensory cortical brain slices. We found that a low number of paired stimulations induces LTP at neocortical layer 4–2/3 synapses. Besides the asymmetric Hebbian STDP reported in the neocortex induced by 100 pairings, we observed a symmetric anti-Hebbian LTD for 50 pairings and unveiled a unidirectional Hebbian spike-timing-dependent LTP (tLTP) induced by 10–15 pairings. This tLTP was not mediated by NMDA receptor activation but requires CB1 receptors and transient receptor potential vanilloid type-1 (TRPV1) activated by endocannabinoids (eCBs). eCBs have been widely described as mediating short- and long-term synaptic depression. Here, the eCB-tLTP reported at neocortical synapses could constitute a substrate operating in the online learning of new associative memories or during the initial stages of learning. In addition, these findings should provide useful insight into the mechanisms underlying eCB-plasticity occurring during marijuana intoxication.
Highlights
In mammals, cardinal cognitive abilities can display very rapid learning dynamics
Noticeable exceptions are studies reporting that single-shock synaptic stimulation of layer 5 neocortical pyramidal neurons induced NMDAR-dependent long-term depression (LTD) in visual cortex (Holthoff et al, 2004) and that single-burst of strong and synchronous inputs from hippocampal CA1 to CA3 triggered NMDAR- and L-type voltage-sensitive calcium channels (VSCCs) dependent long-term potentiation (LTP; Remy and Spruston, 2007)
We report here the existence of a Hebbian coincidence-activity dependent LTP induced by a low number of pairings (∼10), which involved the eCB system. eCB-timing-dependent LTP (tLTP) induction relies on activation of type-1 cannabinoid receptor (CB1R) and transient receptor potential vanilloid type-1 (TRPV1) triggered by coupled rises of calcium mediated by type-5 metabotropic glutamate receptor (mGluR5) and VSCCs
Summary
Cardinal cognitive abilities can display very rapid learning dynamics. Forming new associative memories and behavioral rules can be learned within a few or even a single trial (Schultz et al, 2003; Pasupathy and Miller, 2005; Armstrong et al, 2006; Rutishauser et al, 2006; Whitlock et al, 2006; Tse et al, 2007; Quilodran et al, 2008; Cook and Fagot, 2009; Ito and Doya, 2009; Izquierdo et al, 2016). It was shown that low numbers of paired stimulations (∼20) in spike-timingdependent plasticity (STDP) paradigm (Dan and Poo, 2006; Sjöström et al, 2008; Feldman, 2012), were able to induce spiketiming-dependent potentiation (tLTP) in dissociated culture of hippocampal neurons (Zhang et al, 2009), in cortical slices (Froemke et al, 2006) and in corticostriatal slices (Cui et al, 2015, 2016). These studies revealed that limited occurrences of coincident activity are able to induce bidirectional plasticity, and this needs to be extended to other synapses and cell conditioning paradigms
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