Structural Determinants of Transmission at Large Hippocampal Mossy Fiber Synapses

Abstract

Synapses are the key elements for signal processing and plasticity in the brain. To determine the structural factors underlying the unique functional properties of the hippocampal mossy fiber synapse, the complete quantitative geometry was investigated, using electron microscopy of serial ultrathin sections followed by computer-assisted three-dimensional reconstruction. In particular, parameters relevant for transmitter release and synaptic plasticity were examined. Two membrane specializations were found: active zones (AZs), transmitter release sites, and puncta adherentia, putative adhesion complexes. Individual boutons had, on average, 25 AZs (range, 7-45) that varied in shape and size (mean, 0.1 m 2 ; range, 0.07-0.17 m 2 ). The mean distance between individual AZs was 0.45 m. Mossy fiber boutons and their target structures were mostly ensheathed by astrocytes, but fine glial processes never reached the active zones. Two structural factors are likely to promote synaptic cross talk: the short distance between AZs and the absence of fine glial processes at AZs. Thus, synaptic cross talk may contribute to the efficacy of hippocampal mossy fiber synapses. On average, a bouton contained 20,400 synaptic vesicles; ϳ900 vesicles were located within 60 nm from the active zone, ϳ4400 between 60 and 200 nm, and the remaining beyond 200 nm, suggesting large readily releasable, recycling, and reserve pools. The organization of the different pools may be a key structural correlate of presynaptic plasticity at this synapse. Thus, the mossy fiber bouton differs fundamentally in structure and function from the calyx of Held and other central synapses.

Differential Gating and Recruitment of P/Q-, N-, and R-Type Ca2+Channels in Hippocampal Mossy Fiber Boutons

“…In relative terms, 66% of Ca 2ϩ channels are P/Q-type, 26% N-type, and 8% R-type. As MFBs, on average, have 29.7 active zones at an age comparable with that used in the present study (four fully reconstructed MFBs at P28) (Rollenhagen et al, 2007) (see also Chicurel and Harris, 1992; Acsády et al, 1998), these total channel numbers correspond to 44 P/Q-type channels, 17 N-type chan- nels, and 5 R-type channels per active zone. It will be interesting to compare these numbers with the number of presynaptic particles in MFB freeze-fracture material, which are thought to be primarily Ca 2ϩ channels (Pumplin et al, 1981).…”

Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain

“…mossy boutons that contact interneurons are generally small in size and contain one synapse. In contrast, the synaptic complexes analyzed in this study are composed of a large presynaptic mossy fiber bouton and postsynaptic dendritic excrescence from a CA3 pyramidal cell with multiple synaptic contacts forming between the two (16,17,29). Given the small percentage of new neurons among all of the existing mature DGCs in the adult hippocampus, unlabeled mossy fiber boutons adjacent to GFP ϩ boutons were analyzed and used as a control for mature bouton structure.…”

Morphological plasticity of astroglia: Understanding synaptic microenvironment

“…In contrast, in the hippocampal CA3 region PAPs virtually isolate synapses from the surrounding tissue and hence make spillover almost impossible (Fig. 4B) (Rollenhagen et al, 2007). …”

“…Fine astrocytic protrusions cover presynaptic and postsynaptic structures but do not reach synaptic active zones (red) on spiny excrescences; asterisk (void), location of an adjacent axonal bouton (not shown). Adapted from (Rollenhagen et al, 2007). ( C ) Three‐dimensional reconstruction of an astrocyte fragment (blue) shown with and without adjacent thin (left, grey) and mushroom (right, dark yellow) dendritic spines equipped with PSDs (red).…”