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Kainate receptor function in rodent subcortical visual processing.

Pothecary, C.A.; (2007) Kainate receptor function in rodent subcortical visual processing. Doctoral thesis , University of London. Green open access

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Glutamate is found throughout the central nervous system and has been shown to be an important excitatory neurotransmitter in the visual system. There are two subdivisions of receptor on which this ubiquitous neurotransmitter acts, metabotropic (mGluR) and ionotropic (GluR) glutamate receptors. There are eight sub types of mGluR falling into three groups, and fifteen GluR subunits also divided into three groups. Kainate receptors (KARs) comprise one group of the ionotropic glutamate receptor subdivision. Relay cells of the lateral geniculate nucleus (LGN) are driven and modulated by a variety of NMDA, AMPA and metabotropic receptors. In addition, investigation into the involvement of mGluR, AMPA and NMDA receptor function in the synaptic processing of the superior colliculus (SC) has been well documented. It has been difficult, however, to establish specific KAR function in these brain structures due to lack of pharmacological agents acting solely at kainate receptors. In recent years such agents have become available, thus enabling the present study of GluR5 involvement in visual processing within the SC and LGN. The purpose of this body of work has been to assess the involvement of GluR5-containing Kainate receptors (KARs) in synaptic transmission between retinal ganglion cells (RGCs) and subcortical brain structures involved in the processing of visual information namely the superficial superior colliculus (SSC) and the lateral geniculate nucleus (LGN). The majority of the work focused on the function of KARs in the SSC. To elucidate the involvement of KARs in visual processing, both in vivo and in vitro methods were utilised. In vivo electrophysiology was used for extracellular recording of evoked activity of both SSC and LGN neurons in response to visual stimuli. This was carried out during intravenous injection of GluR5 antagonist. In vivo recording twinned with iontophoretic administration of GluR5-specific pharmacological compounds was also employed to investigate KAR participation in direct synaptic transmission between RGCs and the SSC neurons. The same technique was used to study KAR involvement in the phenomenon of response habituation exhibited by these neurons. To parallel in vivo protocols, in vitro SSC slice experiments were performed to study the effect of GluR5 agonists and antagonists on evoked postsynaptic currents. This enabled the administration of drugs at concentrations specific for GluR5 subunits whilst investigating GluR5 involvement in direct synaptic transmission between RGC input and SSC neurons. In addition, a paired pulse protocol was employed to propose a presynaptic location of GluR5-containing KARs at retinal input into the SSC. Furthermore, the use of GluR5- specific and GABAR-specific compounds during evoked current recording indicated the involvement of GluR5-containing receptors in the direct modulation of excitatory but not inhibitory input into the SSC. In summary, therefore, both in vivo and in vitro electrophysiology techniques were used to indicate a location and function for GluR5 KARs in the subcortical visual system of the rat. GluR5-containing receptors were found to modulate visual processing of both the LGN and SSC. It was unclear whether these receptors were located in the LGN itself due to the use of systemic injection protocols, however, iontophoresis of GluR5-selective drugs demonstrated a role in modulating visual responses within the SSC. The mechanism by which GluR5 receptors modulated responses in the SSC was further elucidated by a series of whole cell patch-clamp experiments which revealed that GluR5-containing receptors reduced synaptic transmission at excitatory inputs directly onto recorded cells and those connections with the intrinsic inhibitory circuitry of the SSC. In addition a paired-pulse protocol was used to determine that the decrease in excitatory transmission was caused by the presynaptic reduction of glutamatergic transmission.

Type: Thesis (Doctoral)
Title: Kainate receptor function in rodent subcortical visual processing.
Identifier: PQ ETD:592329
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis
UCL classification:
URI: https://discovery.ucl.ac.uk/id/eprint/1445016
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