Control of GABA release at single mossy fiber-CA3 connections in the developing hippocampus

Abstract

In this review some of the recent work carried out in our laboratory concerning the functional role of GABAergic signalling at immature mossy fibres (MF)-CA3 principal cell synapses has been highlighted. While in adulthood MF, the axons of dentate gyrus granule cells release onto CA3 principal cells and interneurons glutamate, early in postnatal life they release GABA, which exerts into targeted cells a depolarizing and excitatory action. We found that GABAA-mediated postsynaptic currents (MF-GPSCs) exhibited a very low probability of release, were sensitive to L-AP4, a group III metabotropic glutamate receptor agonist, and revealed short-term frequency-dependent facilitation. Moreover, MF-GPSCs were down regulated by presynaptic GABAB and kainate receptors, activated by spillover of GABA from MF terminals and by glutamate present in the extracellular medium, respectively. Activation of these receptors contributed to the low release probability and in some cases to synapses silencing. By pairing calcium transients, associated with network-driven giant depolarizing potentials or GDPs (a hallmark of developmental networks thought to represent a primordial form of synchrony between neurons), generated by the synergistic action of glutamate and GABA with MF activation increased the probability of GABA release and caused the conversion of silent synapses into conductive ones suggesting that GDPs act as coincident detector signals for enhancing synaptic efficacy. Finally, to compare the relative strength of CA3 pyramidal cell output in relation to their MF glutamatergic or GABAergic inputs in adulthood or in postnatal development, respectively, a realistic model was constructed taking into account different biophysical properties of these synapses.

Neuronal Calcium Wave Propagation Varies with Changes in Endoplasmic Reticulum Parameters: A Computer Model

“…Electrical dynamics in the dendrite followed the standard parallel conductance model. Ion channels were based on a prior model of a hippocampal pyramidal cell (Safiulina et al, 2010) (http://senselab.med.yale.edu/modeldb/ShowModel.asp?model=126814) and included L-, N-, and T-type Ca 2+ channels, which allowed extracellular calcium to enter the dendrite at different voltage levels (McCormick and Huguenard, 1992; Kay and Wong, 1987). The equations for the ion channels follow, leak, Na + and K + currents were represented by the conductance approximation: I ion = g ion · ( V − E ion ) ( g conductance; E reversal potential) using E Na = 50 mV; E k = −77 mV; E leak = −64 mV; ( g leak = 39.4 · 10 −6 S / cm 2 ), while the Goldman-Hodgkin-Katz (GHK) flux equation was used for Ca 2+ currents: I Ca = p Ca · GHK Ca ( p permeability).…”

Reproducibility of the effects of theta burst stimulation on motor cortical plasticity in healthy participants

“…Then, in order to find the best parameters to reliably characterize brain responses to cTBS, we assessed the reproducibility of several physiological markers that have been used in previous studies (Di Lazzaro et al, 2005, 2008; Freitas et al, 2011; Gentner et al, 2008; Huang et al, 2005; Oberman et al, 2010). A spline interpolation was determined for each participant.…”

“…When applied over the primary motor cortex (M1), continuous TBS (cTBS) decreases the amplitude of subsequent motor-evoked potentials (MEPs) for 10–60 min, whereas intermittent TBS (iTBS) increases it (Gentner et al, 2008; Goldsworthy et al, 2012; Huang et al, 2005; Talelli et al, 2007; Zafar et al, 2008). These protocols have been shown to be useful to assess changes in brain plasticity mechanisms related to age (Freitas et al, 2011) or pathology (Oberman et al, 2010). However, it is known that even subtle modifications of the cTBS protocol can influence its effect (for a review see Ridding and Ziemann, 2010).…”

L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat

“…The remaining DA is packaged into vesicles by the type 2 vesicular monoamine transporter (Eisenhofer et al, 2004;Westerink, 2006). Depolarization-induced calcium influx then promotes fusion of vesicles with the plasma membrane and release of DA into the synaptic cleft (Denker and Rizzoli, 2010). …”