Long-Term Potentiation in Distinct Subtypes of Hippocampal Nonpyramidal Neurons

Abstract

We have investigated NMDA receptor-dependent long-term potentiation (LTP) in distinct subtypes of nonpyramidal neurons of the CA1 hippocampus using induction protocols that permitted the differentiation between a direct form of LTP and plasticity resulting simply from the "passive propagation" of LTP occurring on CA1 pyramidal neurons. Two types of stratum (st.) oriens/ alveus interneurons received passive propagation of synaptic potentiation via the recurrent collaterals of CA1 pyramidal cells, but neither subtype possessed direct plasticity. In st. radiatum, two distinct classes of cells were observed: st. radiatum interneurons that showed neither direct nor propagated forms of synaptic plasticity, and "giant cells" for which EPSPs were robustly potentiated after a pairing protocol. This potentiation is similar to the LTP described in pyramidal cells, and its induction requires NMDA receptor activation. Thus, a large heterogeneity of synaptic plasticity exists in morphologically distinct neurons and suggests that complex changes in the CA1 network properties will occur after the induction of LTP.Key words: hippocampus; interneurons; LTP; plasticity; GABAergic; CA1 Synaptic plasticity of the CA1 subfield of the rat hippocampus has been extensively studied and characterized in pyramidal cells (Bliss and Collingridge, 1993;Malenka and Nicoll, 1993;Lisman, 1994). Although many issues still are under debate (Kullmann and Siegelbaum, 1995), the mechanisms involved in the induction of long-term potentiation (LTP) and long-term depression (LTD) have been elucidated (Bliss and Collingridge, 1993;Malenka, 1994). Both forms of plasticity require the activation of postsynaptic NMDA receptors (NMDARs) and an elevation of intracellular calcium levels (Collingridge et al., 1983; Malenka et al., 1988, Dudek andBear, 1992;Mulkey and Malenka, 1992), which lead to phosphorylation or dephosphorylation processes (Malinow et al., 1988;Malenka et al., 1989;Mulkey at al, 1993;Lisman, 1994).At the level of the hippocampal network, the net flow of information in the CA1 region is strongly modulated by the action of the nonpyramidal neurons, the cell bodies of which are distributed throughout all layers of the hippocampus (Lacaille et al., 1987(Lacaille et al., , 1989 Lacaille and Schwartzkroin, 1988a,b;Buhl et al., 1994;Sik et al., 1994Sik et al., , 1995Cobb et al., 1995;Maccaferri and McBain, 1995) (for review, see Freund and Buzsaki, 1996). The vast majority (ϳ90%) of these cells have been shown to be glutamate decarboxylase (GAD)-positive inhibitory interneurons (Woodson et al., 1989), the axons of which target different domains of the pyramidal cell dendritic tree (Gulyás et al., 1993;Buhl et al., 1994;Sik et al., 1995). Therefore, the possibility of additional synaptic plasticity occurring in nonpyramidal cells would greatly increase both the power and the level of complexity of signal processing in the CA1 subfield. Indeed, several reports have shown that after tetanic stimulation, changes occur in (1) evoked nonpyramidal cell f...

Synaptic Communication among Hippocampal Interneurons: Properties of Spontaneous IPSCs in Morphologically Identified Cells

“…radiatum, spiny dendrites located in strata radiatum and lacunosum-moleculare, and its axon projecting to str. oriens (Maccaferri and McBain, 1996) revealed sIPSC kinetics similar to those found in pyramidal cells (Table 1) but with a smaller average amplitude (20.7 pA).…”

“…Recent in vitro and in vivo studies using intracellular labeling methods have identified several hippocampal CA1 interneuron types and have classified them according to their input and output features (Buhl et al, 1994;McBain et al, 1994;Sik et al, 1995;Freund and Buzsáki, 1996;Halasy et al, 1996;Maccaferri and McBain, 1996). Numerous physiological recordings were obtained from interneurons in this hippocampal subfield, but only two groups of dendritic inhibitory cells, namely bistratified cells and O-LM cells (Buhl et al, 1994;McBain et al, 1994;Sik et al, 1995;Halasy et al, 1996), have been morphologically characterized in detail.…”

Nucleus Reuniens Thalami Modulates Activity in Hippocampal Field CA1 through Excitatory and Inhibitory Mechanisms

“…First, electrical stimulation of RE -CA1 afferents at their origin causes an active (subthreshold) depolarization of the apical dendrites of pyramidal cells, which may enhance their state of excitability. Second, RE-elicited spiking of extracellularly recorded units was not detected in the stratum pyramidale but in strata oriens/alveus and radiatum, which indicates synaptic excitation of local nonpyramidal cells that are likely associated with inhibitory mechanisms (Lacaille et al, 1987;Samulack et al, 1993;McBain et al, 1994;Steffensen, 1995;Bergles et al, 1996;Maccaferri and McBain, 1996; for review, see Freund and Buzsáki, 1996). Furthermore, evidence is provided for the existence of a projection from caudal to rostral RE that is considered to form the anatomical substrate underlying the presently observed disynaptic and complex RE-evoked responses in CA1.…”

“…According to their distinctive morphologies, axonal targets, and neurochemical markers, CA1 interneurons in strata oriens/ alveus and radiatum represent a heterogeneous class of nonpyramidal cells (McBain et al, 1994;Buckmaster and Soltesz, 1996;Freund and Buzsáki, 1996;Maccaferri and McBain, 1996). A Figure 6.…”

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

“…Intrinsic inhibitory interneurons in the hippocampus may also control long-term modifications of synaptic strength induced by synaptic transmission (Buzsaki et al 1996;Maccaferri and McBain 1996;Miles et al 1996;Tsubokawa and Ross 1996;McMahon and Kauer 1997;Laezza et al 1999). …”