DIFFERENTIAL RESPONSE DYNAMICS OF CORTICOTHALAMIC GLUTAMATERGIC SYNAPSES IN THE LATERAL GENICULATE NUCLEUS AND THALAMIC RETICULAR NUCLEUS G. M. ALEXANDER, a T. L. FISHER a AND D. W. GODWIN a,b * a The Neuroscience Program, Wake Forest University School of Med- icine, Medical Center Boulevard, Winston-Salem, NC 27157, USA b Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA Abstract—The corticothalamic feedback pathway provides excitatory synaptic input to both the thalamic reticular nu- cleus and the lateral geniculate nucleus. We studied excita- tory postsynaptic currents elicited from corticothalamic stim- ulation in the visual sector of the thalamic reticular nucleus and the lateral geniculate nucleus to compare the response of these neurons to stimulation of their common input path- way. Using whole cell patch clamp recordings in ferret tha- lamic slices, we compared single excitatory postsynaptic current decay kinetics, presynaptic glutamate release dy- namics through paired pulse facilitation and responses to corticothalamic train stimulation. We found that single tha- lamic reticular nucleus excitatory postsynaptic currents were significantly sharper than lateral geniculate nucleus responses. The mean thalamic reticular nucleus excitatory postsynaptic current decay constant () was 4.90.5 ms, while the mean lateral geniculate nucleus excitatory postsynaptic current  value was 11.80.8 ms. Presynaptic release dynamics as measured by responses to paired stimuli were conserved between the thalamic reticular nucleus and lateral geniculate nucleus. However, facilitating responses to train stimulation were markedly different between nuclei. Lateral geniculate nucleus responses showed proportionately larger facilitation (reaching 842.976.4% of excitatory postsynaptic current 1 amplitude) than thalamic reticular nucleus responses (reach- ing 223.144.0% of excitatory postsynaptic current 1 ampli- tude). These data indicate that while the corticothalamic path- way produces excitatory postsynaptic currents in both the thalamic reticular nucleus and lateral geniculate nucleus, other factors uniquely affect the functional integration of the inputs in each nucleus. © 2005 Published by Elsevier Ltd on behalf of IBRO. Key words: EPSC, AMPA, GluR, thalamus, paired pulse facil- itation, desensitization. One of the most compelling issues in thalamic physiology is the role of the massive feedback that thalamic relay neurons receive from their target sensory cortices. In the visual system, synapses derived from the feedback path- way originating in cortical layer VI have been shown to be numerically superior to those provided by retinal ganglion cells (Wilson et al., 1984; Erisir et al., 1997). In addition to dense innervation of lateral geniculate nucleus (LGN) relay neurons, layer VI neurons emit collaterals into the visual sector of the adjacent thalamic reticular nucleus (TRN), which contains only GABAergic neurons that project to the LGN (Montero and Singer, 1984; Robson, 1983). Cortical excitation of TRN cells inhibits LGN cells via inhibitory postsynaptic potentials (IPSPs), with both GABA A and GABA B receptor involvement (Sanchez-Vives and McCor- mick, 1997). This disynaptic inhibitory influence is central to the mechanism of sleep spindles (McCormick and Bal, 1997) and may be selectively involved in active visual processing (Weese et al., 1999; Montero, 2000). Since the LGN and TRN receive common inputs from layer VI neurons, at first glance the influence of corticotha- lamic inputs on LGN and TRN neurons should be similar. However, there are indications that TRN neurons may re- spond differently to this input. For example, TRN cells have been shown to express higher levels of the -amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) recep- tor subunit, GluR4, and therefore show increased sensitivity to corticothalamic excitation than associated relay nuclei (Mineff and Weinberg, 2000; Golshani et al., 2001). Despite the possibility of differing postsynaptic responses to this com- mon input, the relative functional influence of corticothalamic inputs has not been comparatively assessed. In this study, we characterized aspects of excitatory postsynaptic currents (EPSCs) recorded in the LGN and TRN upon corticothalamic stimulation using whole cell patch clamp recordings. We first measured the decay of individual postsynaptic glutamatergic responses from neurons in each nucleus and found them to possess distinctive kinetics. We then compared presynaptic release by using paired pulse stimulation and found that basic release dynamics in response to paired pulses are conserved between the TRN and LGN. However, on assess- ing the responses of LGN and TRN neurons to high fre- quency stimulus trains we observed that the responses to paired pulses did not predict the degree of facilitation to prolonged stimuli. Facilitation at corticogeniculate synapses was more pronounced than that of TRN neurons in response to train stimulation at the same frequency. We conclude that TRN neurons quickly reach maximum facilitation in response to corticothalamic feedback, while LGN neurons show a *Correspondence to: D. W. Godwin, Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Boulevard Winston-Salem, NC 27157, USA. Tel: +1-336-716-9437; fax: +1-336-716-4534. E-mail address: dgodwin@wfubmc.edu (D. W. Godwin). Abbreviations: ACSF, artificial cerebrospinal fluid; AMPA, -amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid; EGTA, ethylene glycol- bis(b-aminoethyl ether)-N,N,N=,N=-tetraacetic acid; EPSC, excitatory postsynaptic current; HEPES, N-[2-hydroxyethyl]piperazine-N=-[2- ethanesulfonic acid]; LGN, lateral geniculate nucleus; NMDA, N-methyl- D-aspartate; PPF, paired pulse facilitation; PPFR, paired pulse facili- tation ratio; TRN, thalamic reticular nucleus; VP, ventroposterior nucleus. Neuroscience 137 (2006) 367–372 0306-4522/06$30.00+0.00 © 2005 Published by Elsevier Ltd on behalf of IBRO. doi:10.1016/j.neuroscience.2005.11.012 367