Lesions of mature barrel field cortex interfere with sensory processing and plasticity in connected areas of the contralateral hemisphere

Abstract

Lesions of primary sensory cortex produce impairments in brain function as an outcome of the direct tissue damage. In addition, indirect lesion effects have been described that consist of functional deficits in areas sharing neural connections with the damaged area. The present study characterizes interhemispheric deficits produced as a result of unilateral lesions of the entire vibrissa representation of S-I barrel field cortex (BFC) in adult rats using single-neuron recording under urethane anesthesia. After unilateral lesions of adult BFC, responses of neurons in the contralateral homotopic BFC are severely depressed. Background (spontaneous) activity is reduced by approximately 80%, responses to test stimuli applied to the whiskers are reduced by approximately 50%, and onset of synaptic plasticity induced by trimming all but two whiskers ("whisker-pairing plasticity") is delayed over sevenfold compared with sham-lesion control animals. These deficits persist with only slight improvement for at least 4 months after lesion. Both fast-spiking and regular-spiking neuron responses are diminished contralateral to the lesion, as are cells above, below, and within the cortical barrels. Enriched environment experience increased the magnitude of responses and accelerated the rate of synaptic plasticity but did not restore response magnitude to control levels. Deficiencies in evoked responses and synaptic plasticity are primarily restricted to areas that share direct axonal connections with the lesioned cortex, because equivalently sized lesions of visual cortex produce minimal deficits in contralateral BFC function. These results indicate that interhemispheric deficits consist of remarkable and persistent decrements in sensory processing at the single-neuron level and support the idea that the deficits are somehow linked to the shared neural connections with the area of brain damage.

Figure 1.

A, Photomicrograph of rat brain coronal section stained for NMDARI subunit showing the extent of a typical ablation lesion of the BFC. B, Schematic diagram of the rat brain showing the location of the BFC lesion, the control lesion in visual cortex (VC), and the recording site in the D2 barrel column of the contralateral hemisphere. C, Schematic diagram showing the pathways from the principal whisker (D2) to its barrel column in the contralateral cortex. Surround whiskers project to their own barrels and activate cells in the D2 barrel column through intracortical pathways.

Figure 2.

Spontaneous and evoked responses of neurons in the D2 barrel column. A, Bar graph showing the level of spontaneous discharges in D2 barrel column neurons in contralateral hemisphere of BFC ablation-lesioned animals and in control animals. The average background activity of neurons from all layers of cortex show an ∼80% decrease in lesioned animals compared with controls. B, Histograms representing mean response magnitudes for 51 neurons from three control animals and 77 neurons from four BFC ablation-lesioned animals. For each neuron, 50 stimuli were applied to each of the three D-row whiskers. Error bars represent SEM. Lesions produced ∼47% reduction in the evoked dischages in the contralateral hemisphere compared with controls. C, Poststimulus time histograms of single-cell responses to principal D2 and surround D1 whisker stimulation contralateral to control and lesion hemispheres (stimulus onset is at 0 msec time point). Note the nearly complete absence of longer-latency spikes as well as the reduction in the short-latency component after a lesion in the contralateral cortex in these single-cell responses.

Figure 3.

Cortical neuron responses to whisker stimulation in controls and in both ablation and excitotoxic NMDA-lesioned animals 8 d after lesion with 7 d of whisker pairing (2-8 d after lesion). A, Histograms showing evoked responses to stimulation of whiskers D1, D2, and D3 in controls and lesioned animals. D2 barrel column neurons in control animals (72 neurons from 3 animals) show a significant increase in response to the principal D2 whisker and a shift in response magnitude from D1:D3 ratio of 1 to being significantly biased toward the active, intact, surround D1 whisker (compare with no whisker-pairing levels in Fig. 2). Both principal and surround whisker responses are reduced after ablation (86 cells, 4 animals) and NMDA lesions (25 neurons, 3 animals). After contralateral barrel field lesions, there is no increase in the principal whisker responses and no shift toward the active surround whisker after 7 d of whisker pairing. B, Segregation of response magnitude into responses in different latency epochs within 3-100 msec after whisker stimulation. Lesions in the opposite hemisphere reduce responses at all latencies, with a particularly marked effect on the short-latency (5-10 and 10-20 msec after stimulus) responses produced by the principal (D2) whisker. (SE on the bars without markers is too small to be seen at this scale.)

Figure 8.

Spontaneous activity levels (spikes per second) of neurons under the nine conditions described in Results. Conditions are identified above each bar. Cortical lesions have a long-lasting negative effect on spontaneous discharges of the neurons in the contralateral hemisphere. EE, Enriched environment; VC, visual cortex; ABL, ablation lesion; days, total survival period with whisker-pairing experience taking place during the last 7 d. Note that only EE for 35 d and nonhomotopic VC lesions produce spontaneous activity in the cortex that is at least within 50% of controls.

Figure 4.

Effect of BFC ablation lesion on fast-spiking and slow-spiking neurons. Separation of barrel column neurons by their spike duration of <0.75 msec (fast-spiking neurons) and ≤0.75 msec (slow-spiking neurons) shows that both neuronal classes are affected by the contralateral BFC lesion. Fast-spiking neurons typically show a higher spontaneous discharge and greater response to whisker stimulation, but both fast- and regular-spiking neurons have reduced responses and fail to show a shift toward the intact surround whisker after 7 d of whisker pairing. Mean response magnitudes of 31 fast-spiking neurons and 55 slow-spiking neurons from lesioned animals were compared with 38 fast-spiking neurons and 34 slow-spiking neurons from control animals (see Fig. 3 from which these data were reclassified).

Figure 5.

Effect of the length of recovery period after BFC ablation lesion on neuronal responses and plasticity in the contralateral barrel cortex. Longer survival times show that, after unilateral BFC lesions, neuronal responses in the contralateral hemisphere do not recover quickly. At each survival time, whisker trimming was done during the 7 d before the end of the 8, 35, or 120 d postlesion period. The animals were kept under standard cage conditions (2 per plastic cage) during the postlesion survival period. Response magnitudes for 86 neurons from 4 rats 8 d after lesion, 30 neurons from 3 rats 35 d after lesion, and 58 neurons from 3 rats 120 d after lesion was compared with the responses from 72 neurons from 3 control animals. There is a clear trend toward higher responses after 4 months, but plasticity fails to return compared with controls. (SE on the bars without markers is too small to be seen at this scale.)

Figure 6.

Effects of lesions in visual cortex on responses in the contralateral BFC. Responses and plasticity in the contralateral BFC are much less affected by visual cortex lesions, with a transient nonsignificant decrease in response magnitude 8 d after lesion (54 neurons from 4 animals), which appear to recover after 35 postlesion days (26 neurons from 2 animals) compared with controls. See Results for additional details.

Figure 7.

Effect of enriched environment experience on the return of function contralateral to BFC lesions in adult rats. The enriched experience was assayed at two postlesion times, 8 d (51 neurons from 3 animals) and 35 d (71 neurons from 3 animals) with the last 7 postlesion days being whisker-paired. After 8 d of enriched experience, the neurons show better responses than after 120 d of regular experience but share the absence of shift toward the intact surround whisker. After 35 d, cortical cell responses are still depressed but are responsive to the whisker-trimming challenge by showing a significant shift (see Results) toward the intact surround whisker.