New intrathalamic pathways allowing modality-related and cross-modality switching in the dorsal thalamus

Abstract

Transmission through the dorsal thalamus involves nuclei that convey different aspects of sensory or motor information. Cells in the dorsal thalamus are strongly inhibited by the GABAergic cells of the thalamic reticular nucleus (TRN). Here we show that stimulation of cells in specific dorsal thalamic nuclei evokes robust IPSCs or IPSPs in other specific dorsal thalamic nuclei and vice versa. These IPSCs are GABA(A) receptor-mediated currents and are consistent with the activation of disynaptic intrathalamic pathways mediated by TRN. Thus, cells engaged in sensory analyses in the ventrobasal complex or the medial division of the posterior complex can interact with cells responsive to sensory events in the caudal intralaminar nuclei, whereas cells engaged in motor analyses in the ventrolateral nucleus can interact with cells responsive to motor events in the rostral intralaminar nuclei. Furthermore, sensory event-related cells in the caudal intralaminar nuclei can interact with motor event-related cells in the rostral intralaminar nuclei. In addition, single cells in one dorsal thalamic nucleus can receive convergent inhibitory inputs after stimulation of cells in two or more other dorsal thalamic nuclei, and TRN-mediated inhibitory inputs can momentarily switch off tonic firing of action potentials in dorsal thalamic cells. Our findings provide the first direct evidence for a rich network of intrathalamic pathways that allows modality-related and cross-modality inhibitory modulation between dorsal thalamic nuclei. Moreover, TRN-mediated switching between dorsal thalamic nuclei could provide a mechanism for the selection of competing transmissions of sensory and/or motor information through the dorsal thalamus.

Fig. 1.

The thalamic slice preparation as it appears in the recording chamber. Transilluminating the slice clearly reveals TRN (R), VB, POm, VL, RIL, CIL, the anteroventral (AV) and mediodorsal (MD) nuclei, and the retroflex fasciculus (asterisk). Thedashed lines indicate the borders of the various nuclei. Rostral is to the top, and medial is to theright. Scale bar, 500 μm.

Fig. 2.

Glutamate stimulation in a sensory or motor dorsal thalamic nucleus evokes IPSCs in cells in another sensory or motor dorsal thalamic nucleus. A, Example of an IPSC recorded from a VB cell in response to glutamate stimulation in CIL (CIL→VB). B, Example of an IPSC recorded from a VL cell in response to glutamate stimulation in RIL (RIL→VL). Calibration also applies to A. C, Example of an IPSC recorded from an RIL cell in response to glutamate stimulation in CIL (CIL→RIL). Glutamate stimulation is indicated by the black bars in A–C. D, The biocytin-filled VB cell from which the recording inA was obtained. E, The biocytin-filled VL cell from which the recording inB was obtained. F, The biocytin-filled RIL cell from which the recording in C was obtained.G, Horizontal section through the thalamus showing the locations of the recorded cell in VB (black dot) shown in D and the stimulation site in CIL (open circle). H, Horizontal section through the thalamus showing the locations of the recorded cell in VL (black dot) shown in E and the stimulation site in RIL (open circle). I, Horizontal section through the thalamus showing the locations of the recorded cell in RIL (black dot) shown in F and the stimulation site in CIL (open circle). Rostral is to thetop, and medial is to the right(G–I). Scale bars:G–I, 500 μm.

Fig. 3.

Stimulation and recording sites are topographically organized between dorsal thalamic nuclei.A, Horizontal section through the thalamus showing Nissl staining. The arrow points to the biocytin-filled RIL cell shown in Figure 5D. The black dotsindicate the borders between RIL and VL (left) and RIL and the mediodorsal nuclei (bottom right).B, Horizontal section through the thalamus showing Nissl staining. The arrow points to the biocytin-filled CIL cell shown in Figure 5H. The black dotsindicate the borders between CIL and POm (left) and CIL and the mediodorsal nuclei (top right). Theasterisk indicates the retroflex fasciculus.C, Horizontal section through the thalamus showing Nissl staining. The arrow points to a biocytin-filled VB cell. The black dots indicate the borders between VB and TRN (top left) and VB and VL (top right).D, Horizontal section through the thalamus showing a summary of the topographic relationship between stimulation sites (arrows) and recording sites (arrows) in various dorsal thalamic nuclei. The corresponding directions of thearrows indicate the locations of the stimulating electrode in one dorsal thalamic nucleus and of cells in another dorsal thalamic nucleus in which a response was evoked. Rostral is to thetop, and medial is to the right(A–D). Scale bars: (in B)A, B, 200 μm; C, 200 μm; D, 500 μm.

Fig. 4.

Bicuculline blocks the IPSCs evoked in cells in one dorsal thalamic nucleus by glutamate stimulation in another dorsal thalamic nucleus. A, Amplitude of IPSCs, evoked in a CIL cell by glutamate stimulation in VB, versus time from an example experiment in which bicuculline was bath applied (black bar). Top, Individual traces taken at the times indicated (1, 2, 3) during the experiment; glutamate stimulation is indicated by the black bars. B, Summary graph of the effect of bicuculline (black bar) on the evoked IPSCs from 10 experiments in which each pair of interacting dorsal thalamic nuclei is represented at least once. Dashed line indicates the baseline response level (100%) in A andB.

Fig. 5.

Glutamate stimulation in two or more dorsal thalamic nuclei evokes IPSCs in single cells in another dorsal thalamic nucleus. A, Examples of IPSCs recorded from a POm cell in response to glutamate stimulation in VB (VB→POm,top trace) and in CIL (CIL→POm, bottom trace). B, The biocytin-filled POm cell from which the recordings in A were obtained.C, Examples of IPSCs recorded from an RIL cell in response to glutamate stimulation in VL (VL→RIL, top trace) and in CIL (CIL→RIL, bottom trace). Glutamate stimulation is indicated by the black bar(top and bottom traces: A,C). Calibration also applies to A.D, The biocytin-filled RIL cell (see Fig.3A) from which the recordings in C were obtained. E, Horizontal section through the thalamus showing the locations of the recorded cell in POm (black dot) shown in B and the stimulation sites in VB (left open circle) and CIL (right open circle). F, Horizontal section through the thalamus showing the locations of the recorded cell in RIL (black dot) shown inD and the stimulation sites in VL (top open circle) and CIL (bottom open circle).G, Examples of IPSCs recorded from a CIL cell in response to glutamate stimulation in VB (VB→CIL, top trace), in POm (POm→CIL, middle trace), and in RIL (RIL→CIL, bottom trace). Glutamate stimulation is indicated by the black bar (top,middle, and bottom traces).H, The biocytin-filled CIL cell (see Fig.3B) from which the recordings in G were obtained. I, Horizontal section through the thalamus showing the locations of the recorded cell in CIL (black dot) shown in H and the stimulation sites in VB (left open circle), POm (bottom middle open circle), and RIL (top right open circle). Rostral is to the top, and medial is to theright (E, F,I). Scale bars: E,F, I, 500 μm.

Fig. 6.

Glutamate stimulation in one dorsal thalamic nucleus interrupts trains of action potentials in cells in another dorsal thalamic nucleus. A, An example of an IPSC recorded from an RIL cell in response to glutamate stimulation (black bar) in CIL (CIL→RIL). B, Horizontal section through the thalamus showing the locations of the recorded cell in RIL (black dot) and the stimulation site in CIL (open circle). Rostral is to thetop, and medial is to the right. Scale bar, 500 μm. C, When held close to −55 mV, the RIL cell responded with a train of action potentials to a depolarizing 0.4 nA current pulse (bottom) injected into the cell.D, A train of action potentials in the RIL cell to the depolarizing current pulse was interrupted by glutamate stimulation (black bar) in CIL.

Fig. 7.

Schematic drawing showing the intrathalamic pathways described here and previously (Crabtree et al., 1998;Crabtree, 1999). These pathways link together cells (black ovals) in VB and POm, VB and CIL, POm and CIL, CIL and RIL, and RIL and VL through cells (black ovals) in TRN.