Reorganization of Corticospinal Projections after Prominent Recovery of Finger Dexterity from Partial Spinal Cord Injury in Macaque Monkeys

We investigated morphologic changes in the corticospinal tract (CST) to understand the mechanism underlying recovery of hand function after lesion of the CST at the C4/C5 border in seven macaque monkeys. All monkeys exhibited prominent recovery of precision grip success ratio within a few months. The trajectories and terminals of CST from the contralesional (n = 4) and ipsilesional (n = 3) hand area of primary motor cortex (M1) were investigated at 5–29 months after the injury using an anterograde neural tracer, biotinylated dextran amine (BDA). Reorganization of the CST was assessed by counting the number of BDA-labeled axons and bouton-like swellings in the gray and white matters. Rostral to the lesion (at C3), the number of axon collaterals of the descending axons from both contralesional and ipsilesional M1 entering the ipsilesional and contralesional gray matter, respectively, were increased. Caudal to the lesion (at C8), axons originating from the contralesional M1, descending in the preserved gray matter around the lesion, and terminating in ipsilesional Laminae VI/VII and IX were observed. In addition, axons and terminals from the ipsilesional M1 increased in the ipsilesional Lamina IX after recrossing the midline, which were not observed in intact monkeys. Conversely, axons originating from the ipsilesional M1 and directed toward the contralesional Lamina VII decreased. These results suggest that multiple reorganizations of the corticospinal projections to spinal segments both rostral and caudal to the lesion originating from bilateral M1 underlie a prominent recovery in long-term after spinal cord injury

Supranormal orientation selectivity of visual neurons in orientation-restricted animals

Altered sensory experience in early life often leads to remarkable adaptations so that humans and animals can make the best use of the available information in a particular environment. By restricting visual input to a limited range of orientations in young animals, this investigation shows that stimulus selectivity, e.g., the sharpness of tuning of single neurons in the primary visual cortex, is modified to match a particular environment. Specifically, neurons tuned to an experienced orientation in orientation-restricted animals show sharper orientation tuning than neurons in normal animals, whereas the opposite was true for neurons tuned to non-experienced orientations. This sharpened tuning appears to be due to elongated receptive fields. Our results demonstrate that restricted sensory experiences can sculpt the supranormal functions of single neurons tailored for a particular environment. The above findings, in addition to the minimal population response to orientations close to the experienced one, agree with the predictions of a sparse coding hypothesis in which information is represented efficiently by a small number of activated neurons. This suggests that early brain areas adopt an efficient strategy for coding information even when animals are raised in a severely limited visual environment where sensory inputs have an unnatural statistical structure

A Primary Role for Nucleus Accumbens and Related Limbic Network in Vocal Tics

トゥレット障害の発症メカニズム解明に新展開 --音声チック症状を呈する霊長類モデルを開発--. 京都大学プレスリリース. 2016-01-21.Inappropriate vocal expressions, e.g., vocal tics in Tourette syndrome, severely impact quality of life. Neural mechanisms underlying vocal tics remain unexplored because no established animal model representing the condition exists. We report that unilateral disinhibition of the nucleus accumbens (NAc) generates vocal tics in monkeys. Whole-brain PET imaging identified prominent, bilateral limbic cortico-subcortical activation. Local field potentials (LFPs) developed abnormal spikes in the NAc and the anterior cingulate cortex (ACC). Vocalization could occur without obvious LFP spikes, however, when phase-phase coupling of alpha oscillations were accentuated between the NAc, ACC, and the primary motor cortex. These findings contrasted with myoclonic motor tics induced by disinhibition of the dorsolateral putamen, where PET activity was confined to the ipsilateral sensorimotor system and LFP spikes always preceded motor tics. We propose that vocal tics emerge as a consequence of dysrhythmic alpha coupling between critical nodes in the limbic and motor networks

Reorganization of corticospinal tract fibers after spinal cord injury in adult macaques.

Previous studies have shown that sprouting of corticospinal tract (CST) fibers after spinal cord injury (SCI) contributes to recovery of motor functions. However, the neuroanatomical mechanism underlying the functional recovery through sprouting CST fibers remains unclear. Here we investigated the pattern of reorganization of CST fibers below the lesion site after SCI in adult macaques. Unilateral lesions were made at the level between the C7 and the C8 segment. The extent of spontaneous recovery of manual dexterity was assessed with a reaching/grasping task. The impaired dexterous manual movements were gradually recovered after SCI. When anterograde tract tracing with biotinylated dextran amine was performed to identify the intraspinal reinnervation of sprouting CST fibers, it was found that the laminar distribution of CST fibers was changed. The sprouting CST fibers extended preferentially into lamia IX where the spinal motor neuron pool was located, to innervate the motor neurons directly. Instead, few, if any, CST fibers were distributed in the dorsal laminae. The present results indicate that CST fibers below the lesion site after SCI in macaques are reorganized in conjunction with the recovery of dexterous manual movements

Treatment With the Neutralizing Antibody Against Repulsive Guidance Molecule-a Promotes Recovery From Impaired Manual Dexterity in a Primate Model of Spinal Cord Injury

脊髄損傷後に指の器用さ回復、サルで抗体治療に成功. 京都大学プレスリリース. 2018-01-09.Axons in the mature mammalian central nervous system have only a limited capacity to grow/regenerate after injury, and spontaneous recovery of motor functions is therefore not greatly expected in spinal cord injury (SCI). To promote functional recovery after SCI, it is critical that corticospinal tract (CST) fibers reconnect properly with target spinal neurons through enhanced axonal growth/regeneration. Here, we applied antibody treatment against repulsive guidance molecule-a (RGMa) to a monkey model of SCI. We found that inhibition of upregulated RGMa around the lesioned site in the cervical cord resulted in recovery from impaired manual dexterity by accentuated penetration of CST fibers into laminae VII and IX, where spinal interneurons and motoneurons are located, respectively. Furthermore, pharmacological inactivation following intracortical microstimulation revealed that the contralesional, but not the ipsilesional, primary motor cortex was crucially involved in functional recovery at a late stage in our SCI model. The present data indicate that treatment with the neutralizing antibody against RGMa after SCI is a potential target for achieving restored manual dexterity in primates

Chemogenetic dissection of a prefrontal-hypothalamic circuit for socially subjective reward valuation in macaques

Abstract The value of one’s own reward is affected by the reward of others, serving as a source for envy. However, it is not known which neural circuits mediate such socially subjective value modulation. Here, we chemogenetically dissected the circuit from the medial prefrontal cortex (MPFC) to the lateral hypothalamus (LH) while male macaques were presented with visual stimuli that concurrently signaled the prospects of one’s own and others’ rewards. We found that functional disconnection between the MPFC and LH rendered animals significantly less susceptible to others’ but not one’s own reward prospects. In parallel with this behavioral change, inter-areal coordination, as indexed by coherence and Granger causality, decreased primarily in the delta and theta bands. These findings demonstrate that the MPFC-to-LH circuit plays a crucial role in carrying information about upcoming other-rewards for subjective reward valuation in social contexts

A causal role for frontal cortico-cortical coordination in social action monitoring

Social interactions require monitoring others’ actions to optimally organise one’s own actions. Here, the authors show that the pathway from the ventral premotor cortex (PMv) to the medial prefrontal cortex (MPFC) is causally involved in monitoring observed, but not executed, actions

Multisynaptic inputs from the medial temporal lobe to V4 in macaques.

Retrograde transsynaptic transport of rabies virus was employed to undertake the top-down projections from the medial temporal lobe (MTL) to visual area V4 of the occipitotemporal visual pathway in Japanese monkeys (Macaca fuscata). On day 3 after rabies injections into V4, neuronal labeling was observed prominently in the temporal lobe areas that have direct connections with V4, including area TF of the parahippocampal cortex. Furthermore, conspicuous neuron labeling appeared disynaptically in area TH of the parahippocampal cortex, and areas 35 and 36 of the perirhinal cortex. The labeled neurons were located predominantly in deep layers. On day 4 after the rabies injections, labeled neurons were found in the hippocampal formation, along with massive labeling in the parahippocampal and perirhinal cortices. In the hippocampal formation, the densest neuron labeling was seen in layer 5 of the entorhinal cortex, and a small but certain number of neurons were labeled in other regions, such as the subicular complex and CA1 and CA3 of the hippocampus proper. The present results indicate that V4 receives major input from the hippocampus proper via the entorhinal cortex, as well as "short-cut" pathways that bypass the entorhinal cortex. These multisynaptic pathways may define an anatomical basis for hippocampal-cortical interactions involving lower visual areas. The multisynaptic input from the MTL to V4 is likely to provide mnemonic information about object recognition that is accomplished through the occipitotemporal pathway