Dopamine D2 Receptors Regulate Collateral Inhibition between Striatal Medium Spiny Neurons.

Rupa R. Lalchandani, Marie-Sophie van der Goes, John G. Partridge, and Stefano Vicini
J Neurosci. 2013 Aug 28;33(35):14075-86. PMID: 23986243

 

Objective:   GABAergic medium spiny neurons (MSNs) make up approximately 95% of all striatal neurons and show extensive local collateral axons.  Different subtypes of these neurons express D1 and D2 dopamine receptors, giving them the potential for differential regulation of subtypes.  This paper examines how chronic dopamine receptor activation results in changes in neuronal morphology and alterations in lateral inhibition through GABAergic transmission.

Methods:    Transgenic mice expressing both td-Tomato under the control of the D1 receptor promoter and EGFP under the control of the D2 receptor promoter were bred and killed at postnatal day 0.  Sections containing striatum had neurons dissociated and cultered with cortical neurons from littermates expressing neither gene and chronically exposed to the D2/3 agnoist quinpirole or the antagonist sulpiride.  Cultured cells were used for whole cell patch clamp of striatal neurons using pipettes filled with 1% biocytin. After recording, slides were fixed for immunohistochemistry.

Results:

·         After 2 weeks of culture, striatal neurons retained reporter expression and cortical neurons developed MSN phenotype.  Some striatal neurons expressed both D1 and D2 reporters and had to be excluded from the study.  Cultured striatal neurons had electrophysiological properties similar to those seen in slices.

·         During dual simultaneous whole-cell recording in voltage clamp, action potentials artificially induced in one cell resulted in inhibitory postsynaptic currents (IPSCs) that were sensitive to the GABAA antagonist BMR and able to be blocked by application of TTX. Additionally, autaptic IPSCs were seen that responded similarly to the drugs.  This demonstrated that the cultured striatal neurons were capable of collateral inhibition through the release of GABA.

·         D2 reporter-expressing MSNs showed an increased number of functional synapses after exposure to D2 agonist. These synapses resulted in more IPSCs that were larger and lasted longer than controls.  The cultured MSNs also had smaller somata, a greater number of primary dendrites, more dendritic branching, and higher expression of GABA transporter and GABAA receptor.  After quinpirole treatment, D2 MSNs showed a larger inhibitory currents in response to GABA application than D1 MSNs or non-treated controls.

·         After quinpirole treatment, D2 MSNs showed a larger inhibitory currents in response to GABA application than D1 MSNs or non-treated controls.

 

-DH