Chapter 13 Differential mechanisms of transmission and plasticity at mossy fiber synapses

Abstract

The last few decades have seen the hippocampal formation at front and center in the field of synaptic transmission. However, much of what we know about hippocampal short-and long-term plasticity has been obtained from research at one particular synapse; the Schaffer collateral input onto principal cells of the CA1 subfield. A number of recent studies, however, have demonstrated that there is much to be learned about target-specific mechanisms of synaptic transmission by study of the lesser known synapse made between the granule cells of the dentate gyrus; the so-called mossy fiber synapse, and its targets both within the hilar region and the CA3 hippocampus proper. Indeed investigation of this synapse has provided an embarrassment of riches concerning mechanisms of transmission associated with feedforward excitatory and inhibitory control of the CA3 hippocampus. Importantly, work from a number of labs has revealed that mossy fiber synapses possess unique properties at both the level of their anatomy and physiology, and serve as an outstanding example of a synapse designed for target-specific compartmentalization of synaptic transmission. The purpose of the present review is to highlight several aspects of this synapse as they pertain to a novel mechanism of bidirectional control of synaptic plasticity at mossy fiber synapses made onto hippocampal stratum lucidum interneurons. It is not my intention to pour over all that is known regarding the mossy fiber synapse since many have explored this topic exhaustively in the past and interested readers are directed to other fine reviews (Henze et al., 2000;Urban et al., 2001;Lawrence et al., 2003;Bischofberger et al., 2006;Nicoll and Schmitz, 2005). Keywordshippocampus; local circuit inhibitory interneuron; long-term depression; glutamate receptors; plasticity; mossy fiber; mGluR7 Anatomy of the granule cell mossy fiber axonBefore discussing the physiological properties of the mossy fiber synapse, a short description of the granule cell anatomy and in particular the mossy fiber axon is warranted. The granule cell is the principal cell of the dentate gyrus and releases the neurotransmitter glutamate (Spruston and McBain, 2006). Granule cells typically possess small, ovoid cell bodies with a single apical, and conical dendritic tree, which extends into the molecular layer and terminates close to the hippocampal fissure. Compared to other principal cells of the hippocampal formation the granule cell is relatively small, possessing a somata approximately 10 μm in *Corresponding author. Tel.: +1 301 4024778; Fax: +1 301 4024777; E-mail: E-mail: mcbainc@mail.nih.gov. Uncited references: Castillo et al. (1994), Chicurel and Harris (1992), Henze et al. (2000), Lei and McBain (2002), Urban et al. (2001), Zucker and Regehr (2002). diameter and about 18 μm along its long axis. The number of dendritic branches is highly variable but the total dendritic length is significantly shorter than their CA1 and CA3 pyramidal neuron counterparts. The axon of the granule cell emerges ...

Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses

“…This conclusion is further substantiated by the suppression of this GABAergic component by focal application of NBQX onto pyramidal cell apical dendrites. Disynaptic IPSCs were observed despite the presence of philanthotoxin, suggesting that excitatory synapses onto hilar and/or CA3 interneurons were not entirely blocked by this antagonist of GluA2-lacking AMPARs (McBain, 2008). Consistent with previous results using paired recordings from unidentified GCs (Mori et al, 2004), our results suggest GAD67ϩ GCs do not evoke monosynaptic IPSCs in their postsynaptic targets upon phasic firing.…”

“…The overall probability of connected cell pairs was 6.0% (n ϭ 39 of 648). In two recordings from CA3 pyramidal cells, the mGluR agonist L-AP4 (20 M) reduced uPSC amplitude by 74.9%, typical of responses originating from MFTs (McBain, 2008).…”

“…Their axons-the mossy fibers (MFs)-convey a complex signal to their postsynaptic targets comprising both monosynaptic, glutamatergic excitation and disynaptic, GABAergic inhibition (McBain, 2008). In addition to glutamate, mossy fiber terminals (MFTs) have been shown to contain GABA (Sandler and Smith, 1991), the GABAsynthesizing enzyme glutamate decarboxylase (GAD; Sloviter et al, 1996), and the vesicular transporter VIAAT (vesicular inhibitory amino acid transporter; Zander et al, 2010).…”

Adult Hippocampal Neurogenesis, Fear Generalization, and Stress

“…The MFB contacts with thorny excrescence-like spines of CA3 pyramidal cells mediate feed-forward excitation (FFE), whereas the disproportionately more numerous filopodial contacts with inhibitory interneurons mediate feedforward inhibition (FFI) onto CA3 pyramidal neurons (Nicoll and Schmitz, 2005). It is thought that a balance between FFE and FFI onto CA3 neurons is required for dictating the temporal window of activation of CA3 neurons, facilitate sparse coding and modulate excitation of the recurrent collateral circuitry of CA3; features long recognized as conducive to pattern separation-completion balance (Treves and Rolls, 1992;O'Reilly and McClelland, 1994;Bragin et al, 1995;McClelland and Goddard, 1996;Acsady and Kali, 2007;McBain, 2008;Cerasti and Treves, 2010;Torborg et al, 2010;Ikrar et al, 2013;Piatti et al, 2013). Furthermore and importantly, decreased FFI connectivity has been associated with increased time dependent loss of memory precision and generalization of fear (Ruediger et al, 2012).…”

Presynaptic LTP and LTD of Excitatory and Inhibitory Synapses

“…MF-SLIN synapses) (for a review, see McBain 2008). Remarkably, the same stimulation paradigm that induces presynaptic LTP in both principal neurons and mossy cells triggers a NMDAR-independent form of presynaptic LTD at some MF-interneuron synapses (Maccaferri et al 1998).…”