Calcium-Permeable AMPA Receptors Provide a Common Mechanism for LTP in Glutamatergic Synapses of Distinct Hippocampal Interneuron Types

Abstract

Glutamatergic synapses on some hippocampal GABAergic interneurons exhibit activity-induced long-term potentiation (LTP). Interneuron types within the CA1 area expressing mutually exclusive molecular markers differ in LTP responses. Potentiation that depends on calcium-permeable (CP) AMPA receptors has been characterized in oriens-lacunosum moleculare (O-LM) interneurons, which express parvalbumin and somatostatin (SM). However, it is unknown how widely CP-AMPAR-dependent plasticity is expressed among different GABAergic interneuron types. Here we examine synaptic plasticity in rat hippocampal O-LM cells and two other interneuron types expressing either nitric oxide synthase (NOS) or cholecystokinin (CCK), which are known to be physiologically and developmentally distinct. We report similar CP-AMPAR-dependent LTP in NOS-immunopositive ivy cells and SM-expressing O-LM cells to afferent fiber theta burst stimulation. The potentiation in both cell types is induced at postsynaptic membrane potentials below firing threshold, and induction is blocked by intense spiking simultaneously with afferent stimulation. The strong inward rectification and calcium permeability of AMPARs is explained by a low level of GluA2 subunit mRNA expression. LTP is not elicited in CCK-expressing Schaffer collateralassociated cells, which lack CP-AMPARs and express high levels of the GluA2 subunit. The results show that CP-AMPAR-mediated synaptic potentiation is common in hippocampal interneuron types and occurs in interneurons of both feedforward and feedback inhibitory pathways.

In Hippocampal Oriens Interneurons Anti-Hebbian Long-Term Potentiation Requires Cholinergic Signaling via α7 Nicotinic Acetylcholine Receptors

“…In addition, our data indicate that in O/A interneurons ␣7 nAChRs can be synaptically activated by endogenous ACh released from cholinergic fibers. Like CP-AMPA receptors, ␣7 nAChRs are highly permeable to calcium (Bertrand et al, 1993;Séguéla et al, 1993;Fucile, 2004) and exhibit a strong inward rectification due to the voltage-dependent block of spermine (Haghighi and Cooper, 1998). Interestingly, nAChRs are several times more sensitive to spermine block than AMPA and kainate receptors (Haghighi and Cooper, 1998).…”

“…This may strongly influence feedback inhibitory circuits, network oscillations and information processing in the hippocampus. Whether nAChRs are instrumental in inducing LTP at glutamatergic synapses of other hippocampal interneuron types known to express calciumpermeable AMPA receptors (Szabo et al, 2012) remain to be established.…”

“…The first one requires the activation of group I metabotropic glutamate receptors (mGluRs) and follows the Hebbian rule of associative learning since it occurs when afferent stimulation coincides with postsynaptic depolarization (Perez et al, 2001;Pelletier and Lacaille, 2008). The second one requires calcium entry via inwardly rectifying calcium-permeable (CP) ␣-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptors and can be induced by hyperpolarizing the postsynaptic neuron during high-frequency stimulation of presynaptic fibers (Lamsa et al, 2007).…”

“…Among different nAChR subtypes, ␣7 nAChRs are highly permeable to calcium (Bertrand et al, 1993;Séguéla et al, 1993;Fucile, 2004) and like CP-AMPA receptors exhibit a strong inward rectification which favors calcium entry at relatively negative membrane potentials (Haghighi and Cooper, 1998). …”

Dendritic Calcium Nonlinearities Switch the Direction of Synaptic Plasticity in Fast-Spiking Interneurons

“…8 D, F; n ϭ 5, p Ͻ 0.05, t test). To test whether the CPA application affects presynaptic Ca 2ϩ release (Simkus and Stricker, 2002;Martín and Buño, 2003), which could contribute to plastic changes, we analyzed the properties of sEPSCs and evoked EPSCs (eEPSC) as well as the area under curve of TBS-evoked somatic responses in control and in the presence of CPA. Our data showed that the amplitude, frequency, and kinetics of sEPSCs were not affected by CPA application (amplitude control: 18.8 Ϯ 0.4 pA; amplitude CPA: 17.7 Ϯ 0.3 pA; frequency control: 5.1 Ϯ 0.8 Hz; frequency CPA: 6.8 Ϯ 1.7 Hz; rise control: 0.36 Ϯ 0.01 ms; rise CPA: 0.35 Ϯ 0.03 ms; decay control: 2.33 Ϯ 0.09 ms; decay CPA: 2.25 Ϯ 0.06 ms; n ϭ 4, p Ͻ 0.05, MannWhitney test).…”