Ultrastructural Localization Suggests that Retinal and Cortical Inputs Access Different Metabotropic Glutamate Receptors in the Lateral Geniculate Nucleus

Abstract

Glutamate has an important neuromodulatory role in synaptic transmission through metabotropic glutamate receptors (mGluRs) linked to a variety of G-protein-coupled second messenger pathways. Activation of these receptors on relay cells in the lateral geniculate nucleus (LGN) with the agonist trans-(1S,3R)-1-amino-1, 3-cyclopentanedicarboxylic acid produces a membrane depolarization that inactivates the low-threshold Ca2+ spike, causing a transition from burst to tonic response mode. The excitatory effects of metabotropic receptor activation in the LGN appear to be produced through the receptors linked to phosphoinositide hydrolysis and apparently only through activation of the corticogeniculate pathway. Two mGluRs, mGluR1alpha (a splice variant of mGluR1) and mGluR5, are linked to the phosphoinositide system. We examined the localization of these receptors with affinity-purified, anti-peptide, polyclonal antibodies raised to the C-terminal region of each receptor protein. Under examination with the light microscope, we found that both types of receptors are present in the geniculate neuropil and in that of the overlying thalamic reticular nucleus, including the perigeniculate nucleus. We also examined the ultrastructural localization of immunolabel with the electron microscope, using a postembedding immunogold marker to identify terminals, dendrites, and somata that contain GABA. Label for the antibody directed against mGluR1alpha was primarily localized in the dendrites of relay cells, postsynaptic to various terminal types. Of these, terminal profiles normally associated with corticogeniculate inputs predominated, whereas retinal terminal profiles were scarce. Label for the antibody directed against mGluR5 label was prominent in inhibitory F2-terminal profiles associated with the retinal input to relay cells. In the perigeniculate nucleus, both mGluRs were localized to dendrites. The distribution of the two phosphoinositide-linked mGluRs in the LGN suggests very different functional roles for the two receptor types. We conclude from these data that mGluR1 appears to have a dominant role in corticogeniculate control of response mode through the feedback glutamatergic pathway from layer VI, whereas mGluR5 is positioned to affect retinogeniculate activation of relay cells through feed forward glomerular interactions.

Metabotropic Glutamate Receptors Differentially Regulate GABAergic Inhibition in Thalamus

“…Furthermore, tetanic stimulation of retinogeniculate fibers, but not corticothalamic fibers, mimicked this increase in inhibition (Govindaiah and Cox, 2004). In this study, we clearly demonstrate that type 5 mGluRs are responsible for this action, which is consistent with anatomical data indicating mGluR 5 localization on F2 terminals (Godwin et al, 1996). In contrast to the mGluR 5 -mediated increase in inhibition, we found that activation of mGluR 2,3 decreased sIPSCs in a TTXinsensitive manner.…”

“…This increase in inhibitory activity resulting from mGluR activation of F2 terminals is insensitive to the Na ϩ -channel blocker tetrodotoxin (TTX) and occurs independent of somatic membrane potential changes in the interneuron (Cox and Sherman, 2000). Considering the diversity of mGluR distribution and variety of mGluR-mediated actions in the thalamus (Godwin et al, 1996;Liu et al, 1998;Cox and Sherman, 1999;Tamaru et al, 2001), we investigated whether specific mGluR subtypes mediate alterations in inhibitory synaptic transmission in the thalamus. Our data suggest that activation of group I mGluRs (mGluR 1,5 ) and group II mGluRs (mGluR 2,3 ) produce distinct physiological actions within the thalamus.…”

Looking back: corticothalamic feedback and early visual processing

“…For example, the type 1 and type 2 metabotropic receptors seem to have different roles in the thalamic circuitry. Type 1 metabotropic glutamate receptors (mGlu 1 receptors) are found on relay-cell distal dendrites that are postsynaptic to axon terminals from cortical layer 6 [28][29][30] (Figure 1b) and, as will be discussed later, they have been implicated in the cortex-mediated effects on geniculate relay cells observed in anaesthetised cats [31]. More recently, in experiments using slices of adult ferret CNS containing the LGN, a presynaptic metabotropic receptor belonging to group II (mGlu 2 ) has been claimed to reduce cortical feedback to the thalamus selectively (Figure 1b).…”

Glutamate receptor functions in sensory relay in the thalamus

“…Electrophysiological studies of these pathways have focused on the role of NMDA receptors (see Scharfman et al 1990;Deschenes & Hu 1990; and, latterly, mGlu receptors (see McCormick & Von Krosigk 1992;Golshani et al 1998;Turner & Salt 2000b;Hughes et al 2002). A particular focus has been the function of mGlu1 receptors, as these have been localized postsynaptically in LGN predominantly beneath terminals of corticothalamic bres (Martin et al 1992;Vidnyanszky et al 1996;Godwin et al 1996). Activation of mGlu receptors in thalamic relay neurons causes a slow depolarizing response associated with an increase in membrane resistance, as seen in many other parts of the brain, probably due a reduction in a potassium conductance (McCormick & Von Krosigk 1992;Turner & Salt 1998;Hughes et al 2002), and this has been shown to be mediated speci cally via mGlu1 receptors ( gure 1) (Turner & Salt 2000b;Hughes et al 2002).…”

“…This offers a multitude of potential signalling and modulatory possibilities for synaptically and extrasynaptically released glutamate (Kullmann 2000). Within the thalamus the distribution of a considerable number of the various glutamate receptors has been described in some detail (Martin et al 1992;Petralia et al 1996;Godwin et al 1996;Liu 1997;Jones et al 1998;Liu et al 1998;Mineff & Valtschanoff 1999;Neto et al 2000;Mineff & Weinberg 2000;Tamaru et al 2001;Bolea et al 2001). This paper seeks to provide a brief overview of some of the well-known synaptic roles of glutamate receptors in the sensory thalamic relay nuclei, and then on the basis of more recent work to indicate other more speculative synaptic roles and how this might relate to sensory transmission through the thalamus under physiological conditions.…”