Heterosynaptic plasticity induced by intracellular tetanization in layer 2/3 pyramidal neurons in rat auditory cortex

Abstract

Key points summary• Learning systems equipped with Hebbian-type associative plasticity are prone to runaway dynamics of synaptic weights and lack mechanisms for synaptic competition; these problems can be resolved by heterosynaptic plasticity: changes at synapses which were not active during the induction.• We show that in layer 2/3 pyramidal neurons from auditory cortex a purely postsynaptic challenge, intracellular tetanization, can induce heterosynaptic plasticity; similar to visual cortex, plasticity direction depends on initial properties of synapses: inputs with initially low release probability tend to potentiate, while those with initially high release probability tend to depress.• Induction of heterosynaptic plasticity requires intracellular Ca 2+ rise and its maintenance involves presynaptic changes, which depend on the nitric oxide signalling pathway.• We conclude that heterosynaptic plasticity is a common property of supragranular pyramidal neurons mediating cortico-cortical connections in both auditory and visual cortices; it may serve as a mechanism of synaptic weight normalization and synaptic competition in these cortical regions.Abstract Associative Hebbian-type synaptic plasticity underlies the mechanisms of learning and memory; however, Hebbian learning rules lead to runaway dynamics of synaptic weights and lack mechanisms for synaptic competition. Heterosynaptic plasticity may solve these problems by complementing plasticity at synapses that were active during the induction, with opposite-sign changes at non-activated synapses. In visual cortex, a potential candidate mechanism for normalization is plasticity induced by a purely postsynaptic protocol, intracellular tetanization.Here we asked if intracellular tetanization can induce long-term plasticity in auditory cortex. We recorded excitatory postsynaptic potentials (EPSPs) of regular (n = 76) and all-or-none (n = 24) type in layer 2/3 pyramidal cells in slices from rat auditory cortex. After intracellular tetanization, 32 of 76 regular inputs (42%) showed long-term depression, 21 inputs (28%) showed potentiation and 23 inputs (30%) did not change. The direction of plasticity correlated with the initial release probability: inputs with initially low release probability tended to be potentiated, while inputs with high release probability tended to be depressed. Thus, intracellular tetanization had a normalizing effect on synaptic efficacy. Induction of plasticity by intracellular tetanization required a rise of intracellular [Ca 2+ ], because it was impaired by chelating intracellular calcium with EGTA. The long-term changes induced by intracellular tetanization involved both preand postsynaptic mechanisms. EPSP amplitude changes were correlated with changes of release indices: paired-pulse ratio and the inverse of the coefficient of variation (CV −2 ). at some all-or-none synapses, changes of averaged response amplitude were correlated with a change of the failure rate, without a change of the synaptic potency, measured as averaged amplitu...

Heterosynaptic Plasticity

“…Disruption of NO signaling in intracellular tetanization experiments did not completely abolish presynaptic changes, implying involvement of additional retrograde signaling systems (Lee and others 2012; Volgushev and others 2000). Activation of metabotropic glutamate receptors (mGluRs) can trigger the production, release, and retrograde action of endocannabinoids, including heterosynaptic LTD at inhibitory synapses (Chevaleyre and Castillo 2003; Chevaleyre and others 2006; Chiu and others 2010; Maejima and others 2001; Pan and others 2008).…”

“…Indeed, the rise of [Ca 2+ ] in is sufficient to induce plasticity (Neveu and Zucker 1996; Yang and others 1999). Induction of long-term heterosynaptic plasticity by intracellular tetanization and other protocols was impaired or blocked by chelation of intracellular calcium with EGTA (Arami and others 2013; Bright and Brickley 2008; Han and Heinemann 2013; Lee and others 2012; Nugent and others 2007). Substantial rise of [Ca 2+ ] in is produced by bursts of back-propagating action potentials activating voltage-dependent calcium channels (Miyakawa and others 1992; Petrozzino and Connor 1994; Schiller and others 1995; Schiller and others 1998; Yuste and Denk 1995), and can be further amplified by calcium release from internal stores (Berridge 1998; Fagni and others 2000; Nakamura and others 1999).…”

“…The resulting profile of [Ca 2+ ] in may promote induction of heterosynaptic LTP at sites of strong calcium rise, and LTD at sites of more moderate rise. However, the final outcome, LTP or LTD, might be also strongly influenced by predispositions of synapses for plasticity, because both potentiation and depression could be induced at synapses presumably located at similar distances and thus experiencing similar calcium rises (Lee and others 2012). …”

“…These effects could be due to diffusion of NO produced at activated synapses (Böhme and others 1991; Gally and others 1990; Hardingham and others 2013; Hölscher and others 1997; O’Dell and Alger, 1991). Disrupting NO signaling by NO-synthase inhibitors and NO-scavengers abolished the dependence of plasticity induced by intracellular tetanization on initial paired-pulse ratio (Lee and others 2012; Volgushev and others 2000). Weaker intracellular tetanization also induced plasticity that was not correlated with initial paired-pulse ratio, suggesting that NO signaling required strong postsynaptic activity (Volgushev and others 2000).…”

Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling

“…It was originally thought that the unstimulated inputs that become weaker do so in the absence of synaptic input, but a careful study of heterosynaptic LTD in the dentate gyrus, the hippocampal region where heterosynaptic LTD has been most successfully studied, showed that spontaneous presynaptic activity is, in fact, required [38]. By contrast, a study of LTD in layer 2/3 pyramidal cells induced heterosynaptic LTD in the slice, where spontaneous input is unlikely [39]. The authors argued that this form of LTD has a role in preventing runaway synaptic modifications in the network and thus may be a form of homeostatic control [40].…”