Advances in the Electrophysiological Recordings of Long-Term Potentiation

Abstract

Understanding neuronal firing patterns and long-term potentiation (LTP) induction in studying learning, memory, and neurological diseases is critical. However, recently, despite the rapid advancement in neuroscience, we are still constrained by the experimental design, detection tools for exploring the mechanisms and pathways involved in LTP induction, and detection ability of neuronal action potentiation signals. This review will reiterate LTP-related electrophysiological recordings in the mammalian brain for nearly 50 years and explain how excitatory and inhibitory neural LTP results have been detected and described by field- and single-cell potentials, respectively. Furthermore, we focus on describing the classic model of LTP of inhibition and discuss the inhibitory neuron activity when excitatory neurons are activated to induce LTP. Finally, we propose recording excitatory and inhibitory neurons under the same experimental conditions by combining various electrophysiological technologies and novel design suggestions for future research. We discussed different types of synaptic plasticity, and the potential of astrocytes to induce LTP also deserves to be explored in the future.

Keywords: LTP; astrocytes; electrophysiological experiments; field potential recording; gliotransmitters; iLTP; single-cell potential recording; tripartite synapses.

Figure 1

Three types of electrophysiological recordings in long-term potentiation (LTP). (A): In vivo optogenetics recordings. (B): In vitro electrode array recording. (C): In vitro whole-cell patch-clamp recordings. (D,E): Traces and normalized slope of excitatory postsynaptic potential or inhibitory postsynaptic current EPSC/IPSC before and after stimulation.

Figure 2

Mechanism of iLTP and the underlying mechanism of astrocyte regulation of iLTP. The red, green, and purple pathways represent the mechanism of NO-mediated long-term potentiation, BDNF-TrkB_iLTP, and NMDAR-dependent _iLTP, respectively. Astrocytes release ATP and D-serine by increasing intracellular calcium ions, which is necessary for NMDA-dependent LTP. Polyamine putrescine (PUT) is an important source of astrocyte GABA production. Significant GABA release suggests that the astrocyte Glu-GABA exchange mechanism is the key to limiting ictal discharge. This evidence may show a new mechanism for regulating iLTP.

Figure 3

Coordinated plasticity of excitatory and inhibitory synapses [55]. LTP induction at a single glutamatergic spine leads to inhibition of nearby GABAergic inhibitory synapses (<3 μm, iLTD), while more distant synapses are enhanced (>3 μm, iLTP), and such GABA_iLTP is heterosynaptic.