A hebbian form of long-term potentiation dependent on mGluR1a in hippocampal inhibitory interneurons

Abstract

Hippocampal inhibitory interneurons play important roles in controlling the excitability and synchronization of pyramidal cells, but whether they express long-term synaptic plasticity that contributes to hippocampal network function remains uncertain. We found that pairing postsynaptic depolarization with -burst stimulation induced long-term potentiation (LTP) of putative singlefiber excitatory postsynaptic currents in interneurons. Either postsynaptic depolarization or -burst stimulation alone failed to induce LTP. LTP was expressed as a decrease in failure rates and an increase in excitatory postsynaptic current amplitude, independent of N-methyl-D-aspartate receptors, and dependent on metabotropic glutamate receptors subtype 1a. LTP was induced specifically in interneurons in stratum oriens and not in interneurons of stratum radiatum͞lacunosum-moleculare. Thus, excitatory synapses onto specific subtypes of inhibitory interneurons express a new form of hebbian LTP that will contribute to hippocampal network plasticity.L ong-term potentiation (LTP) is the enduring increase in strength of synaptic transmission observed after tetanization of afferents (1). This synaptic plasticity has been extensively studied at glutamate synapses onto CA1 pyramidal cells of the hippocampus, where multiple forms of LTP can be induced by activation of N-methyl-D-aspartate receptors (NMDARs) (1, 2), metabotropic glutamate receptors (mGluRs) (3), and voltagedependent Ca 2ϩ channels (4, 5).The hippocampal neuronal network is also composed of inhibitory interneurons, which control the excitability and synchronization of projection cells (6-8). Modeling studies suggest that plasticity at interneuron synapses is important for learning and recall by hippocampal neuronal networks (9). However, experimental evidence of long-term synaptic plasticity at input and͞or output synapses of hippocampal interneurons has been controversial (10-16). This uncertainty has been due, in part, to the heterogeneity of interneuron types present in the hippocampus and to the complexity of the network (6,17,18). An important confounding factor has been that LTP induced at pyramidal cell synapses by tetanic stimulation of Schaffer collaterals can passively propagate to interneurons through recurrent excitatory collaterals of pyramidal cells and can be confused with direct potentiation of excitatory inputs onto interneurons (19). In addition, the apparent absence in interneurons of Ca 2ϩ -calmodulin-dependent protein kinase II and calcineurin (20), two major components of the Ca 2ϩ -signaling cascades involved in the induction of NMDAR-dependent LTP and depression, has been argued to support the lack of synaptic plasticity in interneurons (19,20). Recently, however, long-term depression has been observed at excitatory synapses onto interneurons after trains of high-frequency stimulation, suggesting that synaptic plasticity can indeed occur directly in interneurons (13,15).In the present study, the issue of long-term synaptic plasticity at synapses directly on i...

Metabotropic Glutamate Receptor Type 5-Dependent Long-Term Potentiation of Excitatory Synapses on Fast-Spiking GABAergic Neurons in Mouse Visual Cortex

“…It was reported, however, that LTP at excitatory synapses on basket cells in the dentate gyrus (Alle et al, 2001) and on interneurons in the stratum oriens/alveus or radiatum of the rat hippocampus (Perez et al, 2001;Topolnik et al, 2006) was induced by paired HFS. The present results in the mouse visual cortex seem consistent with the latter three reports.…”

“…Regarding expression sites of LTP of excitatory synapses on inhibitory interneurons, the previous studies in the hippocampus reported the presynaptic expression of LTP (Alle et al, 2001;Perez et al, 2001;Topolnik et al, 2006), although another study reported no change in the paired-pulse ratio of EPSPs of stratum radiatum interneurons, implicating the postsynaptic expression (Lamsa et al, 2005). The present study suggests, for the first time in the visual cortex, that LTP of excitatory synapses on FS-GABA neurons in layer II/III of the cortex may be mainly postsynaptic in origin.…”

Spike-Timing-Dependent Plasticity of Neocortical Excitatory Synapses on Inhibitory Interneurons Depends on Target Cell Type

“…At the synapses between excitatory spiny neurons in layer 4 of rat barrel cortex, correlated spiking also induces only LTD (Egger et al, 1999). Activity-dependent longterm plasticity of excitatory synapses on inhibitory interneurons has been studied more extensively in the hippocampus (McMahon and Kauer, 1997;Cowan et al, 1998;Maccaferri et al, 1998;Laezza et al, 1999;Christie et al, 2000;Toth et al, 2000;Alle et al, 2001;Perez et al, 2001;Lei and McBain, 2002;Lamsa et al, 2005). However, the polarity of synaptic changes and underlying mechanisms remain controversial, presumably because of differences in the type of interneurons involved and in the experimental conditions used, including the LTP/LTD induction paradigms.…”

Timing and Balance of Inhibition Enhance the Effect of Long-Term Potentiation on Cell Firing

“…For instance, either LTD of IPSPs or a change in excitability likely underlies the cases of E-S potentiation that have been reported to occur in the absence of LTP (Bliss and Lomo, 1973;Andersen et al, 1980;Abraham et al, 1985;Taube and Schwartzkroin, 1988;Jester et al, 1995). Nonetheless, whereas E-S potentiation is reliably observed in the hippocampus after tetanus-LTP, studies addressing the issue of tetanus-induced plasticity in the inhibitory branch of the disynaptic circuit have reported a variety of results (McLean et al, 1996;McBain and Maccaferri, 1997;McBain et al, 1999;Gaiarsa et al, 2002), ranging from no changes in inhibition , to LTP of IPSPs (Kairiss et al, 1987;Stelzer et al, 1994;Ouardez and Lacaille, 1995;Xie et al, 1995;Maccaferri and McBain, 1996;Cowan et al, 1998;Shew et al, 2000;Perez et al, 2001) to LTD of IPSPs (McMahon and Kauer, 1997;Lu et al, 2000;Chevaleyre and Castillo, 2003). Although we argue that inhibitory plasticity does not contribute to E-S potentiation when using a relatively mild pairing protocol, it may play a significant role under other induction protocols that more strongly engage the inhibitory circuitry.…”