Developmental Decrease in Short-Term Facilitation at Schaffer Collateral Synapses in Hippocampus Is mGluR1 Sensitive

Abstract

Speed HE, Dobrunz LE. Developmental decrease in short-term facilitation at Schaffer collateral synapses in hippocampus is mGluR1 sensitive. J Neurophysiol 99: 799 -813, 2008. First published November 21, 2007 doi:10.1152/jn.00625.2007. Developmental changes can occur in the dynamic properties of synapses, known as short-term plasticity. Using rat acute hippocampal slices at room temperature, we have previously shown a decrease in short-term facilitation at Schaffer collateral synapses from young adults compared with juveniles in response to temporally complex natural stimulus patterns such as synapses receive in vivo. Here we show that this developmental decrease in facilitation is also seen at 32°C and investigate the underlying mechanism. Addition of the mGluR1 antagonist LY367385 increases short-term facilitation in response to the natural stimulus pattern, showing that mGluR1 is activated by synaptically released glutamate. Although synaptic activation of mGluR1 occurs at both ages, the effect is larger in young adults. Furthermore, blocking mGluR1 eliminates most of the developmental decrease in short-term facilitation during the natural stimulus pattern. We investigated possible retrograde/downstream messengers involved after synaptic activation of mGluR1. Blocking cannabinoid receptors has no effect on the response during the natural stimulus pattern, indicating that the reduction in facilitation during synaptic activation of mGluR1 does not occur through release of endocannabinoids. We find that blocking GABA B receptors increases facilitation during the natural stimulus pattern and occludes the effect of the mGluR1 antagonist, indicating a role for the modulation of GABA release from inhibitory interneurons by mGluR1 activation. These data suggest a model where synaptic activation of mGluR1 on inhibitory interneurons causes an increase in GABA release by inhibitory interneurons, which activates GABA B receptors on Schaffer collateral synapses and inhibits shortterm facilitation during the natural stimulus pattern.

GABAergic Signaling Increases Through the Postnatal Development to Provide the Potent Inhibitory Capability for the Maturing Demands of the Prefrontal Cortex

“…# P \ 0.05 indicated the difference between P16-P19 and P20-P23 in a and asterisks mark significant differences between the two groups linked by line in b, c, * P \ 0.05 or P \ 0.01 (n = 28) group, the significant changes appeared from P12-P15 (n = 18) to P16-P19 group together with from P16-P19 to P20-P23 group (Fig. 4a one-way ANOVA and Post Hoc test, P \ 0.05), which was in accordance with research by Speed and Dobrunz (2008) in hippocampus. In addition, we further took a comparison among the fitted line of STP at last three development stages with F-test (P20-P23, P24-P27, and P [ 27 groups), it was showed that the short-term facilitation induced by the 5-pulse stimulations in P [ 27 group significantly weakened compared with that in P20-P23 group (F-test, P \ 0.05).…”

“…The changes of the 1st eEPSC reflected the intrinsic properties of synapses including synaptic number, synaptic structure primarily, while that of the 5th eEPSC and STP preferred to embody the characters of synaptic network and mechanism of synaptic transmission, especially, based on the studies previously (Reyes and Sakmann 1999;Zucker 1989;Speed and Dobrunz 2008;Zucker and Regehr 2002), it was found that the short-term changes occur via presynaptic mechanisms primarily including the changes in neurotransmitter release and Ca 2? concentration in presynaptic terminal, etc.…”

Distinguishing linear vs. non-linear integration in CA1 radial oblique dendrites: it’s about time

“…Several studies support the assumption of non-saturated NMDARs (Mainen et al, 1999; Mcallister and Stevens, 2000; Nimchinsky et al, 2004). In addition, the bursty firing patterns of CA3 neurons in vivo (Ranck, 1973; Suzuki and Smith, 1985; Tropp-Sneider et al, 2006; Mizuseki et al, 2009), coupled with evidence for reliable axonal propagation (Emptage et al, 1999, 2003; Meeks et al, 2005) and robust short-term synaptic facilitation at Schaffer collateral synapses (Dobrunz et al, 1997; Speed and Dobrunz, 2008), appear ideally suited to deliver the multiple glutamate releases per input “event” that can lead to strong NMDA-dependent post-synaptic responses.…”

Metabotropic Glutamate 1 Receptor: Current Concepts and Perspectives

“…Nevertheless, definitive elucidation of how mGlu1 receptors contribute to the neural mechanisms of associative learning is still missing. However, these effects of mGlu1 receptors may tentatively be ascribed to a modulation of GABAergic transmission involving hippocampal interneurons (Speed and Dobrunz, 2008).…”