Input‐specific learning rules at excitatory synapses onto hippocampal parvalbumin‐expressing interneurons

Abstract

Key points• Parvalbumin-expressing interneurons represent a major source of inhibition of CA1 hippocampal principal cells and influence both spike timing precision and network oscillations.• These interneurons receive both feed-forward and feedback excitatory inputs which recruit them in the hippocampal network.• In this study, we compared the functional properties of these two inputs and how they may be modified by neuronal activity.• We show that calcium-permeable AMPA receptors and NMDA receptors are differentially distributed at feed-forward versus feedback inputs and act as coincidence detectors of opposing modalities.• Our results reveal that the two major excitatory inputs onto CA1 parvalbumin-expressing interneurons undergo long term plasticity with different frequency regimes of afferent activity, which is likely to influence their function under both normal and pathological conditions.Abstract Hippocampal parvalbumin-expressing interneurons (PV INs) provide fast and reliable GABAergic signalling to principal cells and orchestrate hippocampal ensemble activities. Precise coordination of principal cell activity by PV INs relies in part on the efficacy of excitatory afferents that recruit them in the hippocampal network. Feed-forward (FF) inputs in particular from Schaffer collaterals influence spike timing precision in CA1 principal cells whereas local feedback (FB) inputs may contribute to pacemaker activities. Although PV INs have been shown to undergo activity-dependent long term plasticity, how both inputs are modulated during principal cell firing is unknown. Here we show that FF and FB synapses onto PV INs are endowed with distinct postsynaptic glutamate receptors which set opposing long-term plasticity rules. Inward-rectifying AMPA receptors (AMPARs) expressed at both FF and FB inputs mediate a form of anti-Hebbian long term potentiation (LTP), relying on coincident membrane hyperpolarization and synaptic activation. In contrast, FF inputs are largely devoid of NMDA receptors (NMDARs) which are more abundant at FB afferents and confer on them an additional form of LTP with Hebbian properties. Both forms of LTP are expressed with no apparent change in presynaptic function. The specific endowment of FF and FB inputs with distinct coincidence detectors allow them to be differentially tuned upon high frequency afferent activity. Thus, high frequency (>20 Hz) stimulation specifically potentiates FB, but not FF afferents. We propose that these differential,

Induction of Anti-Hebbian LTP in CA1 Stratum Oriens Interneurons: Interactions between Group I Metabotropic Glutamate Receptors and M1 Muscarinic Receptors

“…This NMDAR-independent LTP may be preferentially induced when the postsynaptic cell is maintained at hyperpolarized potentials when Ca 2ϩ entry via Ca 2ϩ -permeable AMPARs should be enhanced, in contrast to the classical Hebbian induction paradigm. Although anti-Hebbian LTP may be induced postsynaptically, it appears to be expressed as an increased probability of glutamate release, similar to NMDAR-independent LTP induced with other protocols (Perez et al, 2001;Nicholson and Kullmann, 2014; but see Le Roux et al, 2013).…”

“…Activa- tion of either receptor affects transient and persistent K ϩ currents. We tested possible effects on the voltage trajectory after interneuron firing (Benardo and Prince, 1982;Greene et al, 1994;Kawasaki et al, 1999;McQuiston and Madison, 1999;Ireland and Abraham, 2002) and on the steady-state membrane potential (Cole and Nicoll, 1983;Madison et al, 1987;Crépel et al, 1994;Guérineau et al, 1995;Howe and Surmeier, 1995;Mannaioni et al, 2001;Lawrence et al, 2006a).…”

“…Interactions between group I mGluRs and M1 mAChRs Group I mGluRs and M1 mAChRs modulate both neuronal excitability (van Hooft et al, 2000;Lawrence et al, 2006b;Park and Spruston, 2012) and synaptic function (Auerbach and Segal, 1996;Palmer et al, 1997), via the Gq protein subunit and downstream pathways. Activation of these receptors has also been implication in the induction of long-term depression at Schaffer collateral synapses made with CA1 pyramidal cells (Volk et al, 2007;Kamsler et al, 2010) and in the short-term depression of synaptic inhibition induced by postsynaptic depolarization (Edwards et al, 2006).…”

“…6). Such cooperation could involve the modulation of multiple conductances including the M-current (I M ), a calcium-activated potassium conductance (I AHP ) mediated by SK channels or a calcium-dependent cationic conductance (I CAT ; Lawrence et al, 2006a;Buchanan et al, 2010;Giessel and Sabatini, 2010). Arguing against nonspecific pharmacological actions, such crossed actions were not evident in effects on miniature EPSC frequency induced by mGluRs and mAChRs (Fig.…”

“…Instead, Ca 2ϩ -permeable AMPARs have been implicated in LTP at glutamatergic synapses made with hippocampal interneurons including those of the CA1 stratum oriens (Lamsa et al, 2007;Szabo et al, 2012) and basket cells (Le Roux et al, 2013). This NMDAR-independent LTP may be preferentially induced when the postsynaptic cell is maintained at hyperpolarized potentials when Ca 2ϩ entry via Ca 2ϩ -permeable AMPARs should be enhanced, in contrast to the classical Hebbian induction paradigm.…”