Leptin Regulation of Synaptic Function at Hippocampal TA-CA1 and SC-CA1 Synapses: Implications for Health and Disease

Gemma McGregor,Jenni Harvey

doi:10.1007/s11064-017-2362-1

Gemma McGregor, Jenni Harvey

Open Access

https://doi.org/10.1007/s11064-017-2362-1

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Journal: Neurochemical Research	Publication Date: Aug 18, 2017
Citations: 28	License type: open-access

Affiliation: Ninewells Hospital, University of Dundee

Abstract

Growing evidence indicates that the endocrine hormone leptin regulates hippocampal synaptic function in addition to its established role as a hypothalamic satiety signal. Indeed, numerous studies show that leptin facilitates the cellular events that underlie hippocampal learning and memory including activity-dependent synaptic plasticity and glutamate receptor trafficking, indicating that leptin may be a potential cognitive enhancer. Although there has been extensive investigation into the modulatory role of leptin at hippocampal Schaffer collateral (SC)-CA1 synapses, recent evidence indicates that leptin also potently regulates excitatory synaptic transmission at the anatomically distinct temporoammonic (TA) input to hippocampal CA1 neurons. The cellular mechanisms underlying activity-dependent synaptic plasticity at TA-CA1 synapses differ from those at SC-CA1 synapses and the TA input is implicated in spatial and episodic memory formation. Furthermore, the TA input is an early target for neurodegeneration in Alzheimer’s disease (AD) and aberrant leptin function is linked to AD. Here, we review the evidence that leptin regulates hippocampal synaptic function at both SC- and TA-CA1 synapses and discuss the consequences for neurodegenerative disorders like AD.

Highlights

Discovery of the obese gene in 1994 via positional cloning techniques enabled insight into the physiological system that controls body weight and energy expenditure [1]
Like cytokines that signal via interaction with janus tyrosine kinases (JAKs), binding of leptin to Ob-R promotes the recruitment and activation of JAK2 leading to phosphorylation of multiple tyrosine residues (Y985, Y1077 and Y1138) within
In parallel studies, chemical (NMDA; 20 μM; 10 min) induction of long-term depression (LTD) in cultured hippocampal neurons reduces the cell surface expression of GluA1-containing amino3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors; an effect that is accompanied by a simultaneous increase in the phosphorylation of JAK2 and STAT3 [69], indicating involvement of JAK–STAT signalling in AMPA receptor internalisation and LTD

Summary

Introduction

Discovery of the obese (ob) gene in 1994 via positional cloning techniques enabled insight into the physiological system that controls body weight and energy expenditure [1]. Leptin-induced LTD requires NMDA receptor, but not mGluR, activation and it occludes low frequency stimulation (LFS)-induced LTD [43] which provides further evidence of a role for leptin in regulating NMDA receptor-dependent synaptic plasticity at SC-CA1 synapses. Leptin-induced LTP evoked at adult hippocampal SC-CA1 synapses is dependent on the synaptic insertion of GluA2-lacking AMPA receptors [47].

Results

Conclusion