Changes in corticothalamic modulation of receptive fields during peripheral injury-induced reorganization

Abstract

The influence of corticothalamic projections on the thalamus during different stages of reorganization was determined in anesthetized raccoons that had undergone previous removal of a single forepaw digit. Single-unit recordings were made from 522 sites in the somatosensory nucleus of the thalamus (ventroposterior lateral nucleus) before and after lesioning parts of primary somatosensory cortex. In those parts of ventroposterior lateral nucleus that had intact input from the periphery, the cortical lesion resulted in an immediate 85% increase in receptive field (RF) size. In animals studied 2-6 weeks after digit amputation, peripherally denervated thalamic neurons had unique RFs that were larger than normal, and these were not further enlarged by cortical lesion. However, at longer periods of reorganization (>4 mo), when the new RFs of denervated neurons had decreased in size, cortical lesion again produced expansion of RF size. These data demonstrate that corticothalamic fibers modulate the spatial extent of thalamic RFs in intact animals, probably by controlling intrathalamic inhibition. This corticothalamic modulation is ineffective during the early stages of injury-induced reorganization when new RFs are being formed, but is reinstated after the new RFs have become stabilized. The fact that neurons in the denervated thalamic region retained their unique RFs after cortical lesion indicates that their new inputs are not being relayed from a reorganized cortex and support the view that some plasticity occurs in or below the thalamus.

Fig. 1.

(A) Diagram of the forepaw representation in raccoon S1 cortex. The cortical lesion included the representational areas for D3 and D5 (hatched). D4 area (shaded) was lesioned and peripherally denervated in the amputation groups. Cr, cruciate sulcus; HL, hindlimb representation; Tr, triradiate sulcus. (B) Photomicrograph showing the VPL thalamic region and several penetrations passing through at the angle indicated by the arrow. (C) Diagram corresponding to B, showing digit regions in VPL. Hatched areas had their corticothalamic input removed. Shaded area 4 was also peripherally denervated.

Fig. 2.

Diagram of the lateral half of the raccoon paw showing RFs (shaded) in representative penetrations passing through the D4 representation of VPL. Examples are from three animals in the control (A), short-term (B), and long-term (C) groups. Each column is from a single penetration from dorsal to ventral through VPL with 200 μm between recording sites. The locations of penetrations and relative depths before (Left) and after (Right) the cortical lesion are only approximately the same.

Fig. 3.

Summary of RF sizes before (open bars) and after (filled bars) cortical lesion. (A–C) The RF size in D4 area of intact (A), short-term (B), and long-term (C) animals. (D) RF size in D3 and D5 regions, which had intact peripheral input but loss of cortical input. (E) RF size in the regions that had intact peripheral and cortical input. Mean ± SEM. The number of recording sites in each group is shown at the bottom of each bar. **, P < 0.01; ***, P < 0.001.

Fig. 4.

Possible circuitry to account for effects of S1 lesion on VPL RF size. (A) In the peripherally intact animal, corticothalamic input inhibits thalamic relay neurons by means of interneurons (IN) and reticular nucleus neurons (RT); cortical lesion produces RF expansion by removing this inhibition (Lower; gray lines indicate reduced activity). (B) At short intervals after amputation of D4, but after new inputs have started to appear from adjacent digits (D3), the thalamic GABAergic neurons are down-regulated (shaded circles) resulting in larger than normal RFs (Upper) and lack of an effect of cortical lesion (Lower). (C) At long intervals after amputation, GABA levels have recovered, leading to smaller, novel RFs (Upper) and expansion after cortical lesion (Lower).