Abstract
Purpose: :
Metabotropic glutamate receptors (mGluRs) are G protein coupled receptors that modulate synaptic transmission. A major obstacle to understanding mGluR function has been the lack of subtype-specific pharmacological agents. Recently, several agonists and allosteric modulators selective for mGluR4, -R7, and -R8 have been developed. The purpose of this study is to examine the function of group-III mGluRs in the inner plexiform layer of the mouse retina.
Methods: :
Extracellular and whole-cell voltage-clamp recordings of mouse ganglion cells were obtained using whole-cell patch electrode techniques in an isolated, superfused retina preparation. Pharmacological manipulations were carried out by adding agents to the bathing medium while monitoring the light responses. We examined the effects of exogenous mGluR agonists, antagonists, and positive allosteric modulators (PAMs) on the magnitude of the currents evoked by a light stimulus. Impulse generation was blocked with QX-314 in the electrode filling solution.
Results: :
When group III-selective mGluR agents were added to the bathing medium, we observed mixed effects on the light-evoked responses of ganglion cells. The mGluR8 PAM AZ12216052 tended to enhance the peak excitatory currents in ON and OFF ganglion cells, but had variable effects on excitatory and inhibitory currents in ON-OFF ganglion cells. The effects tended to be stronger for brighter stimuli. The mGluR4 PAM VU0155041 affected the ganglion cell light responses in a way that was similar but not identical to those of the AZ compound. The mGluR8 agonist DCPG reduced the amplitude of the light-evoked currents in ON, OFF, and ON-OFF ganglion cells.
Conclusions: :
The effects of these compounds on light-evoked currents suggest that different functional mGluRs subtypes are expressed in the circuitry that mediates the responses of different ganglion cell subtypes. Activation of mGluR8 appears to reduce glutamate release from retinal bipolar cells onto several ganglion cell subtypes. Activation of mGluR8 and possibly another mGluR subtypes also appears to suppress the release of an inhibitory neurotransmitter from amacrine cell processes.
Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • excitatory amino acid receptors • ganglion cells