Quantal transmission at mossy fibre targets in the CA3 region of the rat hippocampus

Abstract

Recent anatomical evidence that inhibitory interneurones receive approximately 10 times more synapses from mossy fibres than do principal neurones (Acsády et al. 1998) has led to the re-examination of the extent to which interneurones are involved in CA3 network excitability. Although many of the anatomical and physiological properties of mossy fibre-CA3 interneurone synapses have been previously described (Acsády et al. 1998; Tóth et al. 2000), an investigation into the quantal nature of transmission at this synapse has not yet been conducted. Here, we employed variance-mean (VM) analysis to compare the release probability, quantal size (q) and number of release sites (n) at mossy fibre target neurones in CA3. At six of seven interneurone synapses in which a high concentration of Ca 2+ was experimentally imposed, the variance-mean relationship could be approximated by a parabola. Estimates of n were 1-2, and the weighted release probability in normal Ca 2+ conditions ranged from 0.34 to 0.51. At pyramidal cell synapses, the variance-mean relationship approximated a linear relationship, suggesting that release probability was significantly lower. The weighted quantal amplitude was similar at interneurone synapses and pyramidal cell synapses, although the variability in quantal amplitude was larger at interneurone synapses. Mossy fibre transmission at CA3 interneurone synapses can be explained by a lower number of release sites, a broader range of release probabilities, and larger range of quantal amplitudes than at CA3 pyramidal synapses. Finally, quantal events on to interneurones elicited spike transmission, owing in part to the more depolarized membrane potential than pyramidal cells. These results suggest that although mossy fibre synapses on to pyramidal cells are associated with a larger number of release sites per synapse, the higher connectivity, higher initial release probability, and larger relative impact per quantum on to CA3 interneurones generate strong feedforward inhibition at physiological firing frequencies of dentate granule cells. Given the central role of CA3 interneurones in mossy fibre synaptic transmission, these details of mossy fibre synaptic transmission should provide insight into CA3 network dynamics under both physiological and pathophysiological circumstances.

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

“…The higher probability of release and higher potency of each release site at the filopodial synapse onto inhibitory interneurons (Lawrence et al, 2004), coupled to their interconnectivity, will tend to provide a robust feedforward inhibitory drive to all downstream targets at low (<0.5 Hz) in vivo discharge rates of dentate granule cells (Jung and McNaughton, 1993). This would suggest that at low frequencies at least, the output of the mossy fiber pathway largely drives a net inhibition onto the CA3 network.…”

“…Importantly, this mossy fiber driven activation of CA3 pyramidal cell will arise only in a brief temporal window because the feedforward inhibitory drive to CA3 pyramidal cells will largely constrain the ability of principal cells to fire an action potential in response to its monosynaptic mossy fiber input (Pouille and Scanziani, 2001;Lawrence et al, 2004). Weakening mossy fiber transmission onto inhibitory interneurons will reduce their likelihood of firing an action potential in response to a single mossy fiber input (Toth et al, 2000;Lawrence and McBain, 2003;Lawrence et al, 2004), ultimately contributing to an erosion of the feedforward inhibitory input and the consequent opening of the temporal window for CA3 pyramidal cell action potential initiation. Couple this with the increased probability of transmitter release at potentiated mossy fiber-CA3 pyramidal cell synapses suggests that such a mechanism could exist to increase the net excitation within the CA3 auto-associative network.…”

“…Individual mossy fiber release sites onto principal cells have a low initial release probability (P r = 0.01-0.05) (Jonas et al, 1993). However, because of the large number of release sites per bouton this endows these presynaptic terminals with a high degree of short-term-and frequency-dependent facilitation of transmission (Salin et al, 1996;Toth et al, 2000;Lawrence et al, 2004). In contrast, mossy fiber synapses onto interneurons in stratum lucidum possess a greater than one order of magnitude higher initial release probability (0.1-0.5) (Lawrence et al, 2004).…”

“…However, because of the large number of release sites per bouton this endows these presynaptic terminals with a high degree of short-term-and frequency-dependent facilitation of transmission (Salin et al, 1996;Toth et al, 2000;Lawrence et al, 2004). In contrast, mossy fiber synapses onto interneurons in stratum lucidum possess a greater than one order of magnitude higher initial release probability (0.1-0.5) (Lawrence et al, 2004). This relatively high release probability endows these filopodial synapses with either mild facilitation or depression in response to brief stimulus trains (Toth et al, 2000).…”

Quantal Size Is Independent of the Release Probability at Hippocampal Excitatory Synapses

“…Alternatively, two-photon imaging of calcium transients in single spines (Oertner et al, 2002;Nimchinsky et al, 2004) and imaging of the destaining rate of FM1-43 fluorescence (Murthy et al, 1997) have been used to monitor P r independently of electrophysiological recordings. It is widely accepted that short-term plasticity is accompanied by changes in P r (for review, see Thomson, 2000;Zucker and Regehr, 2002); however, whether alterations in P r (purely presynaptic) fully account for such plasticity (Gulyas et al, 1993;Paulsen and Heggelund, 1994;Stevens and Wang, 1995;Hanse and Gustafsson, 2001;Silver et al, 2003;Lawrence et al, 2004) or whether postsynaptic alterations also occur (Otis et al, 1996;Rozov and Burnashev, 1999;Oleskevich et al, 2000;Oertner et al, 2002;Harrison and Jahr, 2003) is still a question of active debate. To determine the quantal parameters and the locus of alterations during short-term facilitation at cortical glutamatergic synapses, we took advantage of the robust facilitation of synapses made by hippocampal CA1 pyramidal cells (PCs) onto specific subtypes of interneurons (Ali and Thomson, 1998;Scanziani et al, 1998;Losonczy et al, 2002).…”