Biomedical subjects

C A Pothecary

Publications and source records attributed to C A Pothecary.

4 recordsLinked to original sources

PubMed2005

Changes in glutamate receptor function in synaptic input to the superficial superior colliculus (SSC) with aging and in retinal degeneration in the Royal College of Surgeons (RCS) rat.

Ionotropic and metabotropic glutamate receptors mediate and modulate retinocollicular transmission. The Royal College of Surgeons (RCS) dystrophic strain of rats suffers from a progressive retinal degeneration with age and hence loss of visual function. We investigated whether this loss of function is accompanied by functional changes in a central target of retinal axons, the superficial superior colliculus (SSC). Field potential recordings were made in SSC slices from RCS rats aged either 4-7 weeks or 33-52 weeks. Blockade of GABAergic transmission revealed a field EPSP in response to optic tract stimulation which was sensitive to the NMDA antagonist AP5. In normal non-dystrophic rats the contribution of NMDA receptors to the fEPSP declined with age, whereas in dystrophic animals no such decline was seen. As mGluR8 may be located on terminals of retinal axons, we also assessed the function of this receptor. The mGluR8 agonist DCPG reduced fEPSPs in normal and dystrophic rats in both age groups to a similar extent, although the effect of DCPG declined with age. These findings indicate that the contribution of NMDA receptors to retinocollicular transmission declines with age in normal rats, but that such a decline is not seen in dystrophic rats which have severely reduced visual function. As NMDA receptors are associated with neural plasticity, it may be that this finding represents an increased residual potential for plasticity in dystrophic rats which may be functionally important.

Aging↗

PubMed2005

Modulation of retino-collicular transmission by Group III metabotropic glutamate receptors at different ages during development.

Group III metabotropic glutamate receptors (especially mGlu4, mGlu7, mGlu8) are thought to be involved in modulating visual processing in the adult superior colliculus, a major termination site of retinal input in the rodent brain. We have investigated this role by making field EPSP recordings in response to optic tract stimulation in superior colliculus slices taken from rats aged from P14 to P180. Application of the Group III agonist L-AP4 at a concentration (10 microM) effective to activate mGlu4 and mGlu8 receptors, but not mGlu7 receptors, resulted in reductions of the field EPSP in all ages, although the effect was greatest in slices taken from P14 rats. Increasing the L-AP4 concentration to 100 microM so as to also activate mGlu7 receptors resulted in further field EPSP reductions. Similar reductions were seen in the combined presence of the GABA antagonists picrotoxin and CGP55845A, indicating a lack of involvement of GABAergic mechanisms in the action of L-AP4. Pairing of optic tract stimuli (20 ms separation) resulted in paired-pulse depression at all ages. L-AP4 was found to reduce paired-pulse depression at both 10 microM and 100 microM in slices from all ages of rat. The results of this study suggest that mGlu4/mGlu8 and mGlu7 receptors modulate retino-tectal transmission via a presynaptic mechanism, and that these effects are greatest in young animals. This is the first demonstration of a functional change in Group III receptor effect with aging, and this would be consistent with developmental regulation of these receptors.

Age Factors↗

PubMed2002

Group I metabotropic glutamate receptors (mGluRs) modulate visual responses in the superficial superior colliculus of the rat.

Group I metabotropic glutamate receptors (mGluRs) are expressed in cells in the superficial layers of the rat superior colliculus (SSC) and SSC afferents. The purpose of this study was to investigate the physiological effect of Group I mGluR activation on visual responses of SSC neurones using both in vivo and in vitro techniques. In the in vivo preparation, agonists and antagonists were applied by iontophoresis and single neurone activity was recorded extracellularly in anaesthetised rats. Application of the Group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) resulted in a reversible inhibition of the visual response. The effect of DHPG could be blocked by concurrent application of the Group I (mGluR1/mGluR5) antagonist (S)-4-carboxyphenylglycine (4CPG) or mGluR1 antagonist (+)-2-methyl-4-carboxyphenylglycine (LY367385). Application of 4CPG alone resulted in a facilitation of the visual response and this effect was not changed when the visual stimulus contrast was varied. Response habituation was observed when visual stimuli were presented at 0.5 s intervals, but this was not affected by DHPG or 4CPG. In slices of the superior colliculus, stimulation of the optic tract resulted in a field EPSP recorded from the SSC whose duration was increased in the presence of the GABA antagonists picrotoxin and CGP55845. Application of DHPG (5-100 microM) reduced the field EPSP, and this effect could be reversed by the mGluR1 antagonist LY367385 (200 microM), but not by the mGluR5 antagonist MPEP (5 microM). These data show that activation of mGluR1, but probably not mGluR5, can modulate visual responses of SSC neurones in vivo, and that this could be via presynaptic inhibition of glutamate release from either retinal or, possibly, cortical afferents.

Amino Acids↗

PubMed2002

Reduction of excitatory transmission in the retino-collicular pathway via selective activation of mGlu8 receptors by DCPG.

We have previously shown that activation of Group III metabotropic glutamate (mGlu) receptors modulates synaptic transmission in the superior colliculus. We thus investigated the effect of the selective mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG) on excitatory synaptic transmission in the superficial superior colliculus (SC) using an in vitro slice preparation of the rat SC. Field EPSPs evoked by optic tract stimulation under conditions of GABA receptor blockade were reduced by DCPG by up to 67.8+/-5.46% (EC(50) 1.25+/-0.56 microM), and this effect could be antagonised by LY341495 at a concentration (300 nM) known to be effective at mGlu8 receptors but not at mGlu4 or mGlu7 receptors. The broad-spectrum (mGlu4/mGlu7/mGlu8) agonist L-2-amino-4- phosphonobutyric acid (L-AP4) produced similar reductions of synaptic transmission (maximal reduction 68.6+/-2.33%; EC(50) 5.7+/-2.61 microM). These data are consistent with previous results which show that mGlu8 receptor activation can reduce synaptic transmission in the spinal cord, and indicate that similar mechanisms operate in other brain areas. Furthermore, this indicates that the mGlu8 receptor may have a role in the modulation of visual transmission in the superior colliculus.

Animals↗