Plasticity of Metabotropic Glutamate Receptor-Dependent Long-Term Depression in the Anterior Cingulate Cortex after Amputation

Abstract

Long-term depression (LTD) is a key form of synaptic plasticity important in learning and information storage in the brain. It has been studied in various cortical regions, including the anterior cingulate cortex (ACC). ACC is a crucial cortical region involved in such emotion-related physiological and pathological conditions as fear memory and chronic pain. In the present study, we used a multielectrode array system to map cingulate LTD in a spatiotemporal manner within the ACC. We found that low-frequency stimulation (1 Hz, 15 min) applied onto deep layer V induced LTD in layers II/III and layers V/VI. Cingulate LTD requires activation of metabotropic glutamate receptors (mGluRs), while L-type voltage-gated calcium channels and NMDA receptors also contribute to its induction. Peripheral amputation of the distal tail impaired ACC LTD, an effect that persisted for at least 2 weeks. The loss of LTD was rescued by priming ACC slices with activation of mGluR1 receptors by coapplying (RS)-3,5-dihydroxyphenylglycine and MPEP, a form of metaplasticity that involved the activation of protein kinase C. Our results provide in vitro evidence of the spatiotemporal properties of ACC LTD in adult mice. We demonstrate that tail amputation causes LTD impairment within the ACC circuit and that this can be rescued by activation of mGluR1.

Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain

“…Two major forms of LTD have been characterized in the hippocampus; one form is triggered by the activation of NMDARs, and the other is triggered by the activation of mGluRs 90 . Both forms of LTD have also been observed in the rodent ACC [91][92][93] (FIG. 2).…”

“…2). Low-frequency stimulation (1-5 Hz) for a prolonged period (3-15 min) induces input-specific LTD in the ACC that requires the activation of mGluR1 and L-VGCCs 91,92 , whereas antagonism of NMDARs has only a minor effect on the induction of this form of LTD 92 . However, an NMDAR-dependent form of LTD in the ACC has also been observed in studies that used a pairing protocol 93,94 ; this form of LTD is sensitive to both GluN2A-and GluN2B-preferring antagonists and requires an increase in postsynaptic Ca 2+ and CaM levels 65,93 .…”

Pharmacological Rescue of Cortical Synaptic and Network Potentiation in a Mouse Model for Fragile X Syndrome

“…Before use, the surface of the MED64 probe was treated with 0.1% polyethyleneimine (Sigma, St Louis, MO; P-3143) in 25 mmol/l borate buffer (pH 8.4) overnight at room temperature. Then, the probe surface was rinsed three times with sterile distilled water (Kang et al, 2012;Liu et al, 2013).…”

“…Coronal brain slices (300 mm) from Fmr1 WT or KO mice, containing the ACC, were prepared using standard methods (Kang et al, 2012). After cutting, slices were then incubated in a submerged recovery chamber with oxygenated (95% O 2 and 5% CO 2 ) artificial cerebrospinal fluid (ACSF) containing (in mM) 124 NaCl, 4.4 KCl, 2 CaCl 2 , 1 MgSO4, 25 NaHCO 3 , 1 NaH 2 PO 4 , and 10 glucose at room temperature for at least 1.5 h.…”

“…In the present study, to investigate possible contributions of FMRP to L-LTP at both synaptic and network levels, we used a 64-channel multielectrode array recording system (MED64) to record L-LTP in the ACC of adult Fmr1 KO and wild-type (WT) mice. In the MED64 system, stable long-term field potentials can be recorded at multiple channels of the same ACC slices (Kang et al, 2012). It provides the unique method to study L-LTP within the local circuit of ACC.…”