The thalamocortical (TC) neurones of the sensory thalamic nuclei receive three excitatory inputs: two are the ascending input from the sensory pathway and the descending input from the cortex, and the third is the modulatory input from the brainstem activating system (Jones, 1985). 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. Using an in vitro slice preparation of the rat dorsal lateral geniculate nucleus (dLGN), the properties of retinogeniculate and corticothalamic inputs to thalamocortical (TC) neurones were examined in the absence of GABAergic inhibition. 2. The retinogeniculate EPSP evoked at low frequency (û 0·1 Hz) consisted of one or two fastrising (0·8 ± 0·1 ms), large-amplitude (10·3 ± 1·6 mV) unitary events, while the corticothalamic EPSP had a graded relationship with stimulus intensity, owing to its slower-rising (2·9 ± 0·4 ms), smaller-amplitude (1·3 ± 0·3 mV) estimated unitary components. 3. The retinogeniculate EPSP exhibited a paired-pulse depression of 60·3 ± 5·6 % at 10 Hz, while the corticothalamic EPSP exhibited a paired-pulse facilitation of > 150 %. This frequency-dependent depression of the retinogeniculate EPSP was maximal after the second stimulus, while the frequency-dependent facilitation of the corticothalamic EPSP was maximal after the fourth or fifth stimulus, at interstimulus frequencies of 1-10 Hz. 4. There was a short-term enhancement of the û 0·1 Hz corticothalamic EPSP (64·6 ± 9·2 %), but not the retinogeniculate EPSP, following trains of stimuli at 50 Hz. 5. The û 0·1 Hz corticothalamic EPSP was markedly depressed by the non-NMDA antagonist 1-(4-amino-phenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazepine (GYKI 52466), but only modestly by the NMDA antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ((RS)-CPP), and completely blocked by the co-application of GYKI 52466, 6_cyano-7-nitroquinoxaline-2,3-dione (CNQX), (RS)-CPP and (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK_801). Likewise, the corticothalamic responses to trains of stimuli (1-500 Hz) were greatly reduced by this combination of ionotropic glutamate receptor antagonists. 6. In the presence of GYKI 52466, CNQX, (RS)-CPP and MK_801, res...

1. The mechanism underlying a novel form of input signal amplification and bistability was investigated by intracellular recording in rat and cat thalamocortical (TC) neurones maintained in slices and by computer simulation with a biophysical model of these neurones. 2. In a narrow membrane potential range centred around −60 mV, TC neurones challenged with small (10-50 pA), short (50-200 ms) current steps produced a stereotyped, large amplitude hyperpolarization ( > 20 mV) terminated by the burst firing of action potentials, leading to amplification of the duration and amplitude of the input signal, that is hereafter referred to as input signal amplification. 3. In the same voltage range centred around −60 mV, single evoked EPSPs and IPSPs also produced input signal amplification, indicating that this behaviour can be triggered by physiologically relevant stimuli. In addition, a novel, intrinsic, low frequency oscillation, characterized by a peculiar voltage dependence of its frequency and by the presence of plateau potentials on the falling phase of low threshold Ca¥ potentials, was recorded. 4. Blockade of pure Na¤ and K¤ currents by tetrodotoxin (1 ìÒ) and Ba¥ (0·1-2·0 mÒ), respectively, did not affect input signal amplification, neither did the presence of excitatory or inhibitory amino acid receptor antagonists in the perfusion medium. 5. A decrease in [Ca¥]ï (from 2 to 1 mÒ) and an increase in [Mg¥]ï (from 2 to 10 mÒ), or the addition of Ni¥ (2-3 mÒ), abolished input signal amplification, while an increase in [Ca¥]ï (from 2 to 8 mÒ) generated this behaviour in neurones where it was absent in control conditions. These results indicate the involvement of the low threshold Ca¥ current (IT) in input signal amplification, since the other Ca¥ currents of TC neurones are activated at potentials more positive than −40 mV. 6. Blockade of the slow inward mixed cationic current (Ih) by 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium chloride (ZD 7288) (100-300 ìÒ) did not affect the expression of the large amplitude hyperpolarization, but abolished the subsequent repolarization to the original membrane potential. In this condition, therefore, input signal amplification was replaced by bistable membrane behaviour, where two stable membrane potentials separated by 15-30 mV could be switched between by small current steps. 7. Computer simulation with a model of a TC neurone, which contained only IT, Ih, K¤ leak current (ILeak) and those currents responsible for action potentials, accurately reproduced the qualitative and quantitative properties of input signal amplification, bistability and low frequency oscillation, and indicated that these phenomena will occur at some value of the injected DC if, and only if, the 'window' component of IT (IT,Window) and the leak conductance (gLeak) satisfy the relation (dIT,WindowÏdV)max > gLeak. 8. The physiological implications of these findings for the electroresponsiveness of TC neurones are discussed, and, as IT is widely expressed in the central nervous syste...

The action of ethosuximide (ETX) on Na+, K+, and Ca2+ currents and on tonic and burst-firing patterns was investigated in rat and cat thalamic neurons in vitro by using patch and sharp microelectrode recordings. In thalamocortical (TC) neurons of the rat dorsal lateral geniculate nucleus (LGN), ETX (0.75-1 mM) decreased the noninactivating Na+ current, INaP, by 60% but had no effect on the transient Na+ current. In TC neurons of the rat and cat LGN, the whole-cell transient outward current was not affected by ETX (up to 1 mM), but the sustained outward current was decreased by 39% at 20 mV in the presence of ETX (0.25-0.5 mM): this reduction was not observed in a low Ca2+ (0.5 mM) and high Mg2+ (8 mM) medium or in the presence of Ni2+ (1 mM) and Cd2+ (100 microM). In addition, ETX (up to 1 mM) had no effect on the low-threshold Ca2+ current, IT, of TC neurons of the rat ventrobasal (VB) thalamus and LGN and in neurons of the rat nucleus reticularis thalami nor on the high-threshold Ca2+ current in TC neurons of the rat LGN. Sharp microelectrode recordings in TC neurons of the rat and cat LGN and VB showed that ETX did not change the resting membrane potential but increased the apparent input resistance at potentials greater than -60 mV, resulting in an increase in tonic firing. In contrast, ETX decreased the number of action potentials in the burst evoked by a low-threshold Ca2+ potential. The frequency of the remaining action potentials in a burst also was decreased, whereas the latency of the first action potential was increased. Similar effects were observed on the burst firing evoked during intrinsic delta oscillations. These results indicate an action of ETX on INaP and on the Ca2+-activated K+ current, which explains the decrease in burst firing and the increase in tonic firing, and, together with the lack of action on low- and high-threshold Ca2+ currents, the results cast doubts on the hypothesis that a reduction of IT in thalamic neurons underlies the therapeutic action of this anti-absence medicine.

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