A restricted lesion of the hand area in the primary motor cortex (M1) leads to a deficit of contralesional manual dexterity, followed by an incomplete functional recovery, accompanied by plastic changes in M1 itself and in other cortical areas on both hemispheres. Using the marker SMI-32 specific to pyramidal neurons in cortical layers III and V, we investigated the impact of a focal unilateral M1 lesion (hand representation) on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres in nine adult macaque monkeys compared with four intact control monkeys. The M1 lesion induced a consistent interhemispheric asymmetry in density of SMI-32-positive neurons in F3 layer V (statistically significant in 8 of 9 lesioned monkeys), highly correlated with the lesion volume and with the duration of functional recovery, but not with the extent of functional recovery itself. Such interhemispheric asymmetry was neither present in the intact monkeys, as expected, nor in F6 in all monkeys. In addition, the M1 lesion also impacted on the basal dendritic arborization of F3 layer V neurons. Neuronal density was clearly less affected by the M1 lesion in F3 layer III compared with layer V. We interpret the remote effect of M1 lesion onto the density of SMI-32-positive neurons and dendritic arborization in the SMAs bilaterally as the consequence of multiple factors, such as changes of connectivity, diaschisis and various mechanisms involved in cortical plasticity underlying the functional recovery from the M1 lesion. SIGNIFICANCE STATEMENT The motor system of macaque monkeys, in addition to be similarly organized as in humans, is a good candidate to study the impact of a focal lesion of the main contributor to voluntary movements, the primary motor cortex (M1), on non-primary motor cortical areas also involved in manual dexterity, both at behavioral and structural levels. Our results show that a unilateral permanent lesion of M1 hand area in nine monkeys affects the interhemispheric balance of the number of SMI-32-positive pyramidal neurons in the cortical layer V of the supplementary motor area, in a way strongly correlated to the lesion volume and duration of the incomplete functional recovery.

Motor cortical areas from both hemispheres play a role during functional recovery after a unilateral spinal cord injury (SCI). However, little is known about the morphological and phenotypical differences that a SCI could trigger in corticospinal neurons of the ipsilesional and contralesional hemisphere. Using an SMI-32 antibody which specifically labeled pyramidal neurons in cortical layers V, we investigated the impact of a unilateral cervical cord lesion on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres of eight adult macaque monkeys compared with four intact control monkeys. We observed in F3 (but not in F6) interindividual variable and adaptive interhemispheric asymmetries of SMI-32 positive layer V neuronal density and dendritic arborization, which are strongly correlated with the extent of the SCI as well as the duration of functional recovery, but not with the extent (percentage) of functional recovery. Significance statement 1. This study consists in a precise quantification on two different levels of the histological consequences on the long term of a traumatic and sudden unilateral interruption of the corticospinal tract at cervical level in 8 non-human primates (adult macaque monkeys). 2. The lesion affected the density and the morphology of layer v pyramidal neurons in the supplementary motor area (SMA), in the form of an interhemispheric adaptive asymmetry, correlated to the lesion size and duration of functional recovery. 3. These changes are reminiscent of those observed in SMA after unilateral lesion of the primary motor cortex, suggesting to some extent comparable mechanism of functional motor recovery from unilateral cortical or spinal lesion. 4. The dendritic arborization in the basal dendrites of the SMI-32 positive neurons in layer V showed a more prominent interhemispheric effect of the lesion than the apical dendrites. Contestabile et al.

The decision to approach or avoid a conspecific is fundamental for survival. Affiliative (prosocial) interactions favor approach behaviors, while antagonistic (aggressive) contacts trigger avoidance. Here we ask how the brain encodes the valence of social interaction. We focused on the nucleus accumbens (NAc), a brain region implicated in social reward processing. We observed that social interactions activate D1-expressing medium spiny neurons (D1-MSNs) regardless of their valence. However, afferent D1- expressing neurons of the anterior insular cortex (AIC) exhibited distinct activity patterns coding for prosocial and aggressive social interaction, respectively. As a result, distinct forms of synaptic plasticity were elicited at the AIC to NAc synapses. Thus, the valence of social interaction induces distinct neural activity in the AIC, which teaches the animal to approach and avoid conspecifics in the future.

The decision to approach or avoid a conspecific is fundamental for survival. Affiliative (prosocial) interactions favor approach behaviors, while antagonistic (aggressive) contacts trigger avoidance. Here we ask how the brain encodes the valence of social interaction. We focused on the nucleus accumbens (NAc), a brain region implicated in social reward processing. We observed that social interactions activate D1-expressing medium spiny neurons (D1-MSNs) regardless of their valence. However, afferent D1- expressing neurons of the anterior insular cortex (AIC) exhibited distinct activity patterns coding for prosocial and aggressive social interaction, respectively. As a result, distinct forms of synaptic plasticity were elicited at the AIC to NAc synapses. Thus, the valence of social interaction induces distinct neural activity in the AIC, which teaches the animal to approach and avoid conspecifics in the future.