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Papers of the Week

Papers: 7 Jan 2023 - 13 Jan 2023

Animal Studies

2022 Dec 05


Function of excitatory periaqueductal grey synapses in the ventral tegmental area following inflammatory injury.


Manipulating the activity of ventral tegmental area dopamine (VTA DA) neurons can drive nocifensive reflexes, and their firing rates are reduced following noxious stimuli. However, the pain-relevant inputs to the VTA remain incompletely understood. In this study, we used male and female mice in combination with identified dopamine and GABA neurons in the VTA that receive excitatory inputs from the periaqueductal grey (PAG), a nexus of ascending pain information. We tested whether PAG-VTA synapses undergo functional plasticity in response to a pain model using optical stimulation in conjunction with slice electrophysiology. We found that acute carrageenan inflammation does not significantly affect the strength of excitatory PAG synapses onto VTA DA neurons. However, at the PAG synapses on VTA GABA neurons, the subunit composition of NMDA receptors is altered; the complement of NR2D subunits at synaptic sites appears to be lost. Thus, our data support a model in which injury initially alters synapses on VTA GABA neurons. Over time, these alterations may increase tonic inhibition of VTA DA neurons leading to their reduced firing.Following a focal injury, the firing rate of dopamine neurons of the ventral tegmental area (VTA) decreases, despite a lack of direct innervation from the periphery. Here we assess the functional changes between a primary node of nociceptive output, the periaqueductal gray (PAG), and the VTA after peripheral inflammation. We find that synaptic strength at PAG-to-VTA dopamine neuron synapses is unaffected following inflammatory injury, but find a change in subunit composition of NMDARs at PAG synapses on the inhibitory neurons of the VTA.