Coexistence of glutamatergic spine synapses and shaft synapses in substantia nigra dopamine neurons.

Miae Jang,Jinyoung Jang,Hyun Jin Kim,Ki Bum Um,Myoung Kyu Park,Sungkwon Chung,Hana Cho

doi:10.1038/srep14773

Miae Jang, Jinyoung Jang + Show 5 more

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https://doi.org/10.1038/srep14773

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Abstract

Dopamine neurons of the substantia nigra have long been believed to have multiple aspiny dendrites which receive many glutamatergic synaptic inputs from several regions of the brain. But, here, using high-resolution two-photon confocal microscopy in the mouse brain slices, we found a substantial number of common dendritic spines in the nigral dopamine neurons including thin, mushroom, and stubby types of spines. However, the number of dendritic spines of the dopamine neurons was approximately five times lower than that of CA1 pyramidal neurons. Immunostaining and morphological analysis revealed that glutamatergic shaft synapses were present two times more than spine synapses. Using local two-photon glutamate uncaging techniques, we confirmed that shaft synapses and spine synapses had both AMPA and NMDA receptors, but the AMPA/NMDA current ratios differed. The evoked postsynaptic potentials of spine synapses showed lower amplitudes but longer half-widths than those of shaft synapses. Therefore, we provide the first evidence that the midbrain dopamine neurons have two morphologically and functionally distinct types of glutamatergic synapses, spine synapses and shaft synapses, on the same dendrite. This peculiar organization could be a new basis for unraveling many physiological and pathological functions of the midbrain dopamine neurons.

Highlights

Large central neurons such as hippocampal pyramidal neurons, cerebellar Purkinje neurons, and many cortical pyramidal neurons, form glutamatergic synapses predominantly on small membranous protrusions called dendritic spines for compartmentalized signal processing[14,15]
It was recently reported that dopamine-specific transgenic mouse line exhibits dramatic non-dopamine specific expression patterns in some parts of the VTA nuclei[28], in our TH-enhanced green fluorescent protein (eGFP) mouse line all of GFP-expressing neurons (n = 1 2) recorded from the substantia nigra pars compacta (SNc), showed the typical electrophysiological properties of dopamine neurons (Fig. S1)
It has been reported that dopamine neurons in the midbrain are involved in many kinds of brain function such as action selection, volitional movement, goal-oriented behavior, reinforcement learning, and reward processing[1,2,49,50], as well as many neuropsychiatric diseases such as Parkinson’s disease, schizophrenia, and drug addiction[51,52,53]

Summary

Introduction

Large central neurons such as hippocampal pyramidal neurons, cerebellar Purkinje neurons, and many cortical pyramidal neurons, form glutamatergic synapses predominantly on small membranous protrusions called dendritic spines for compartmentalized signal processing[14,15]. In the present study, we used high-resolution two-photon confocal microscopy in the mouse midbrain slices, to examine morphological features of dendrites and glutamatergic synapses in the nigral dopamine neurons. We provide the first evidence that the midbrain dopamine neuron is a particular type of neuron that possesses a substantial number of two morphologically and functionally distinct glutamatergic synapses, spine synapses and shaft synapses, on the same dendrite. This characteristic organization of glutamatergic synapses could be an important base for further studies of dopamine neuron functions

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