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. The processing of sensory information by the CNS is complicated by the complex interconnections between subcortical and cortical areas. Connections between the thalamus and cortex are largely reciprocal (1) with information being processed in both feed-forward (periphery to thalamus to cortex) and feedback (corticothalamic) directions. Although the majority of studies have concentrated on the ascending or feed-forward system, the feedback connections are actually much more numerous than the thalamocortical axons (1) and may contribute to focusing of information processing in the visual (2), auditory (3, 4), and somatosensory thalamus (5). Recently it has been proposed that this feedback from the cortex may contribute to plasticity in the ventroposterior lateral (VPL) nucleus, the main thalamic relay in the somatosensory system (6-8).The corticothalamic axons are excitatory, glutamatergic, and reciprocally focused on the thalamic neurons that project to the same cortical region (1). In addition to exciting thalamocortical relay neurons directly, they also produce inhibition by means of local ␥-aminobutyric acid (GABA)ergic interneurons, which are present in most species but not rats (9), and GABAergic neurons of the reticular thalamic nucleus, which project back into VPL (10). Electrophysiological studies have confirmed the monosynaptic excitatory and disynaptic inhibitory responses in VPL relay cells when cortical output cells are stimulated (11). Studies on the function of this fe...

Cortical influences on sizes and rapid plasticity of tactile receptive fields in the dorsal column nuclei

“…Unlike PO, VP is dependent on the DCN for tactile inputs; thus, it is plausible that cortex has identical influences on sizes of DCN and VP RFs. Acute loss of cortical inputs causes a range of immediate effects on sizes of normal VP RFs, including substantial RF enlargements (Yuan et al, 1985;Ergenzinger et al, 1998;Krupa et al, 1999;Chowdhury et al, 2004), whereas the present results show that DCN RFs underwent no or small size changes after acute loss of cortical inputs. This suggests that RF enlargements in VP are not copies of similar substantial RF enlargements in the DCN, a possibility that has been discussed, but left unaddressed, in VP studies (Ergenzinger et al, 1998;Chowdhury et al, 2004).…”

“…Acute loss of cortical inputs causes a range of immediate effects on sizes of normal VP RFs, including substantial RF enlargements (Yuan et al, 1985;Ergenzinger et al, 1998;Krupa et al, 1999;Chowdhury et al, 2004), whereas the present results show that DCN RFs underwent no or small size changes after acute loss of cortical inputs. This suggests that RF enlargements in VP are not copies of similar substantial RF enlargements in the DCN, a possibility that has been discussed, but left unaddressed, in VP studies (Ergenzinger et al, 1998;Chowdhury et al, 2004). Differing from cortico-DCN inputs from layer V, cortico-VP inputs originate entirely from layer VI (Bourassa et al, 1995;Veinante et al, 2000;Killackey and Sherman, 2003).…”

“…In addition, there is topographical variation in densities of cortical input terminals across DCN locations, and dorsal DCN areas where neurons with cutaneous RFs on paws are located have, at the light microscopic level, dense peripheral input terminals but sparse to moderate cortical terminals (Cheema et al, 1983;Maslany et al, 1991;Desbois et al, 1999). Although further quantification of synapses from identified sources is needed, from existing data it is possible that high densities of peripheral and other subcortical inputs to the DCN underlie strong subcortical influences on sizes of DCN RFs, much like high densities of corticothalamic inputs contribute to strong cortical influences on sizes of VP RFs (Liu et al, 1995;Ergenzinger et al, 1998;Jones, 2002;Chowdhury et al, 2004).…”

“…Normal thalamic RFs were commonly thought to be dictated by ascending projections. However, it has been shown that acute lesion or inactivation of somatosensory cortex triggers a range of immediate effects on sizes of normal VP RFs, including significant RF enlargements (Yuan et al, 1985;Ergenzinger et al, 1998;Krupa et al, 1999;Chowdhury et al, 2004). In addition to effects on RFs in VP, acute block of cortical activity causes loss of tactile responses and related normal RFs in the thalamic posterior nucleus (PO; Diamond et al, 1992).…”

AMPA and GABAA/B receptor subunit expression in the cuneate nucleus of adult squirrel monkeys during peripheral nerve regeneration

“…This has substantial influence on receptive field expression at lower levels of the ascending neuroaxis [1,2, 3,5, 34, 35, 38, 39, 40, 54, 56 57, 58]. While corticofugal feedback does play an important role in both immediate unmasking and reorganization within subcortical structures [6, 13, 17, 27, 31, 58], the time-course and extent of changes occurring in the brainstem impose important limitations on cortical reorganization.…”