Sensory input and burst firing output of rat and cat thalamocortical cells: the role of NMDA and non‐NMDA receptors.

Abstract

1. Intracellular and patch-clamp recordings were obtained from thalamocortical (TC) cells in the rat and cat dorsal lateral geniculate nucleus (dLGN) in vitro to study the role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the synaptic potential and burst firing evoked by electrical stimulation of the optic tract. 2. At membrane potentials more positive than -65 mV, the sensory synaptic potential consisted of a fast EPSP that was followed by a smaller, slower component. At membrane potentials more negative than -65 mV, this slower component became more prominent owing to the presence of a low-threshold (LT) Ca2+ potential, which in turn evoked a high-frequency (> 150 Hz) burst of action potentials. The lower, but not the upper limit of the range of membrane potential over which burst firing occurred was dependent on the amplitude of the fast EPSP. 3. The non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM) and 1-(4-amino-phenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3- benzodiazepine (GYKI 52466, 100 microM) greatly depressed the fast EPSP, abolished the burst firing generated by the LT Ca2+ potential, and left a relatively small, slow EPSP, which was sensitive to the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (DL-AP5, 50-100 microM). 4. In the absence of CNQX or GYKI 52466, DL-AP5 depressed the slow but not the fast EPSP. DL-AP5 also increased the latency of the first action potential evoked by the LT Ca2+ potential or even abolished the LT Ca2+ potential and associated burst firing. The latter effect was only present when this type of firing occurred within a small membrane potential range. 5. DL-AP5 had no effect on the properties of the LT Ca2+ current IT, indicating that its effect on the burst firing was not mediated by a direct action on IT. 6. The response of TC cells to high-frequency (100 Hz) stimulation consisted of an initial burst firing response, followed by a sustained depolarization that could reach firing threshold. This sustained depolarization was markedly depressed by DL-AP5 but not by CNQX. 7. These results demonstrate that with low-frequency stimulation of the sensory afferents, the generation of TC cell output in the rat and cat dLGN is mainly controlled by non-NMDA receptors, while the contribution of NMDA receptors is limited to the burst firing generated by the LT Ca2+ potential, and depends on the membrane potential range over which this type of firing occurs.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterization of sensory and corticothalamic excitatory inputs to rat thalamocortical neurones in vitro

“…(1) The stimulation at low frequency of corticothalamic fibres passing through the NRT evoked an EPSP in rat dLGN TC neurones with similar pharmacology to that evoked by stimulation of retinogeniculate fibres (Turner et al 1994). (2) These retinogeniculate and corticothalamic EPSPs differed in terms of their latency to onset, rising phase, stimulus intensity-response relationship, and response to paired stimuli, consistent with the differences in synapse location, fibre input and the previously noted frequency-dependent synaptic mechanisms observed with the corticothalamic input (Jones, 1985;Deschênes & Hu, 1990).…”

“…0, 0·10 Hz; 1, 1·00 Hz; þ, 3·33 Hz; ±, 10·0 Hz. that exhibited by the retinogeniculate EPSP, which was also predominantly mediated by non-NMDA excitatory amino acid receptors, with the NMDA component able to modulate EPSP-evoked burst firing (Scharfman et al 1990;Turner et al 1994;Paulsen & Heggelund, 1994).…”

“…The sensory and cortical inputs form synapses at different locations on the dendritic arbors of TC neurones, with the sensory input more proximal to the soma and the cortical input more distal. The sensory input to auditory, somatosensory and visual thalamic nuclei has been well characterized as being mediated by both non-NMDA and NMDA ionotropic glutamate receptors both in vitro (Scharfman, Lu, Guido, Adams & Sherman, 1990; Turner, Leresche, Guyon, Soltesz & Crunelli, 1994;Hu, Senatorov & Mooney, 1994;Kao & Coulter, 1997) and in vivo (Salt, 1986;Sillito, Murphy & Salt, 1990a;Sillito, Murphy, Salt & Moody, 1990b;Salt & Eaton, 1991). However, while the contribution of these ionotropic glutamate receptors to corticothalamic synaptic transmission has been established both in vitro and in vivo (Deschênes & Hu, 1990;Scharfman et al 1990;Eaton & Salt, 1996;Kao & Coulter, 1997) 1.…”

Mechanisms Underlying Signal Filtering at a Multisynapse Contact

“…Error bars indicate SEM. and the more hyperpolarized potentials (Ϫ70 to Ϫ90 mV; "deep potentials") as the "burst mode" (Turner et al, 1994;Blitz and Regehr, 2003). At deep potentials, EPSPs elicited by the small fiber input were unable to generate any spikes, whereas the larger fiber input generated one or more spikes (Fig.…”

The Role of Calcium Channels in Epilepsy

“…If the membrane is sufficiently depolarized, then the subsequent activation of both sodium and potassium channels can initiate high-frequency firing or "burst firing," the proposed pathophysiological substrate for the spike and wave discharges (SWDs) seen on electroencephalographic (EEG) recordings, in which the "spike" represents AP firing and the "wave" corresponds to a period of relative neuronal inactivity (Coulter et al 1989a;Turner et al 1994;Kim et al 2001;Chemin et al 2002;Blumenfeld 2005;Molineux et al 2006;Xu and Clancy 2008;Alvina et al 2009;Cain and Snutch 2012). In addition, T-type channels generate "window currents," in which, at certain potentials, a proportion of channels are open but not inactivated, leading to an inward calcium current, which contributes to membrane stability.…”