Biology subjects

Sanderson, T. M.

Publications and source records attributed to Sanderson, T. M..

3 recordsLinked to original sources

bioRxiv2025

Activation of CP-AMPARs is required for homosynaptic and heterosynaptic structural LTP in the hippocampus

Long-term potentiation (LTP) involves alterations in synaptic structure that are believed to underlie the persistent increase in synaptic efficacy. Here we compared structural LTP (sLTP) in EGFP-labelled spines with functional LTP, using field potential recording, at CA3-CA1 synapses in mouse hippocampal slices for [~] 2 h following theta-burst stimulation (TBS). Activity-dependent labelling with FM4-64 allowed us to compare activated (FM+) and non-activated synapses and thereby compare homo- and hetero-synaptic sLTP. In addition, we related spine volume changes according to the probability of release, P(r), of activated synapses. At homosynaptic sites there was the expected NMDA receptor (NMDAR)-dependent potentiation of spine volume that persisted throughout the recording period. We found that this sLTP also required the synaptic activation of CP-AMPARs. There was also sLTP at heterosynaptic sites that, surprisingly, developed more quickly than the associated homosynaptic sLTP. This heterosynaptic sLTP was also dependent on the synaptic activation of both NMDARs and CP-AMPARs. Additionally, we observed a trans- and hetero-synaptic interaction, whereby the heterosynaptic spines grew according to the P(r) of the neighbouring active (homosynaptic) synapse. These observations have therefore advanced our understanding of sLTP in several ways; the first demonstration of the absolute requirement for the synaptic activation of CP-AMPARs for sLTP; the magnitude of heterosynaptic sLTP relative to homosynaptic sLTP and the hitherto unexpected combination of trans- and hetero-synaptic interactions.

neuroscience↗

bioRxiv2024

Activation of group I mGluRs is required for heterosynaptic priming of long-term potentiation in mouse hippocampus

Metaplasticity involves changes in the state of neurons or synapses that influence their ability to generate synaptic plasticity. One form of heterosynaptic metaplasticity, known as synaptic tagging and capture (STC), has been intensively studied but the underlying mechanisms are not fully understood. In experiments using hippocampal slices prepared from C57BL/6J mice, we have examined the role of group I metabotropic glutamate receptors (mGluRs) in STC. We used a version of STC where a strong theta-burst stimulus (TBS), delivered to one set of Schaffer collateral-commissural pathway inputs to CA1, preceded a weak TBS delivered to a second independent set of inputs. We observed that, firstly, dual inhibition of mGluR1 and mGluR5, using YM 298198 and MTEP respectively, did not affect a form of protein synthesis-independent LTP (LTP1), but substantially inhibited a form of protein synthesis-dependent LTP (LTP2). Secondly, these inhibitors prevented the small heterosynaptic potentiation, which is often associated with LTP2. Thirdly, STC was abolished when these antagonists were applied either during the strong (priming) TBS or during the subsequent weak TBS at the independent pathway. It is proposed that the activation of group I mGluRs serves as a trigger for local protein synthesis both during the strong and weak TBS and, as such, are an integral part of the STC process. STC is involved in associative learning and memory, a cognitive function that is disrupted in many brain disorders including Alzheimers disease.

neuroscience↗

bioRxiv2020

PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus

Long-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance ({gamma}). Here we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involved purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA was activated, resulted in LTP that was associated with a transient increase in {gamma} (LTP{gamma}). This {gamma} increase was due to the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII was necessary and sufficient for LTPN whilst PKA was additionally required for LTP{gamma}. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.

neuroscience↗