Long‐term depression of synaptic transmission in the adult mouse insular cortex in vitro

Abstract

The insular cortex (IC) is known to play important roles in higher brain functions such as memory and pain. Activity-dependent long-term depression (LTD) is a major form of synaptic plasticity related to memory and chronic pain. Previous studies of LTD have mainly focused on the hippocampus, and no study in the IC has been reported. In this study, using a 64-channel recording system, we show for the first time that repetitive low-frequency stimulation (LFS) can elicit frequency-dependent LTD of glutamate receptor-mediated excitatory synaptic transmission in both superficial and deep layers of the IC of adult mice. The induction of LTD in the IC required activation of the N-methyl-d-aspartate (NMDA) receptor, metabotropic glutamate receptor (mGluR)5, and L-type voltage-gated calcium channel. Protein phosphatase 1/2A and endocannabinoid signaling are also critical for the induction of LTD. In contrast, inhibiting protein kinase C, protein kinase A, protein kinase Mζ or calcium/calmodulin-dependent protein kinase II did not affect LFS-evoked LTD in the IC. Bath application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine produced another form of LTD in the IC, which was NMDA receptor-independent and could not be occluded by LFS-induced LTD. Our studies have characterised the basic mechanisms of LTD in the IC at the network level, and suggest that two different forms of LTD may co-exist in the same population of IC synapses.

ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion

“…These are referred to as activated channels. Consistent with the previous study39, low-frequency stimulation (LFS) in insular cortical slices from WT mice induced a significant depression of fEPSPs in the majority of activated channels (Fig. 1c; Supplementary Fig.…”

“…We then examined a variety of synaptic plasticity models using a previously established 64-channel multi-electrode array (MED64) recording system3839, with the MED64 probe placed within the insular cortical slice as shown in Fig. 1a,b.…”

“…However, the molecular and synaptic mechanisms underlying CTA memory extinction3637 remain undetermined. Here we examine the role of ASIC1a in synaptic plasticity in the adult mouse insular cortex using multiple-electrode array slice recording3839, and CTA learning and extinction by behavioural assessment. We found that in contrast to the established role for ASIC1a in LTP, which promotes associative learning and memory in other brain areas61621, ASIC1a is a critical modulator of long-term depression (LTD) in the insular cortex and this function is important for the extinction of the acquired taste aversion memory.…”

Metabotropic glutamate receptor dependent long-term depression in the cortex

“…In the CA1 region of the hippocampus, paired-pulse LFS (PP-LFS) activates Group I mGluRs and M1 muscarinic acetylecholine receptors [151819]. However, in some cortical regions, such as the anterior cingulate cortex (ACC) and insular cortex (IC), 900 single pulses in 1 Hz induce LTD that are fully blocked by (S)-α-methyl-4-carboxyphenylglycine (MCPG), which is an antagonist to Groups I and II mGluRs [202122]. In addition, there are also other unique protocols such as the application of mGluR agonists and electrical stimulation with tetanus [2324] or using weaker LFS and maintaining the postsynaptic potential at –40 mV which is called the pairing protocol [2526].…”

“…Two studies [2164] was performed in a manner similar to that of Kang et al 2012. Recordings were done throughout all the layers in the IC and was plotted as superficial (layer I~II/III) and deep layer (layer V~VI).…”