Neuronal activity reorganization in motor cortex for successful locomotion after a lesion in the ventrolateral thalamus

Thalamic stroke leads to ataxia if the cerebellum-receiving ventrolateral thalamus (VL) is affected. The compensation mechanisms for this deficit are not well understood, particularly the roles that single neurons and specific neuronal subpopulations outside the thalamus play in recovery. The goal of this study was to clarify neuronal mechanisms of the motor cortex involved in mitigation of ataxia during locomotion when part of the VL is inactivated or lesioned. In freely ambulating cats, we recorded the activity of neurons in layer V of the motor cortex as the cats walked on a flat surface and horizontally placed ladder. We first reversibly inactivated approximately 10% of the VL unilaterally using glutamatergic transmission antagonist CNQX and analyzed how the activity of motor cortex reorganized to support successful locomotion. We next lesioned 50-75% of the VL bilaterally using kainic acid and analyzed how the activity of motor cortex reorganized when locomotion recovered. When a small part of the VL was inactivated, the discharge rates of motor cortex neurons decreased, but otherwise the activity was near normal, and the cats walked fairly well. Individual neurons retained their ability to respond to the demand for accuracy during ladder locomotion; however, most changed their response. When the VL was lesioned, the cat walked normally on the flat surface but was ataxic on the ladder for several days post-lesion. When ladder locomotion normalized, neuronal discharge rates on the ladder were normal, and the shoulder-related group was preferentially active during the stride's swing phase.

Exercise Fatigue Induce the Oxidative Stress and the Expression of mGluR 4 and mGluR 5 on the Ventrolateral Thalamus in Rats

Objective: The motor thalamus plays an important role during exercise. It aims to observe the changes of mGluR4 and mGluR5 in ventrolateral thalamus of rats induced by repeated exhaustive exercise, and to discuss the relationship of mGluR4, mGluR5 and oxidative damage occured during exhaustive exercise. Methods: There were 48 male wistar rats, which were randomly divided into four groups including CG, 0EG, 24EG and 48 EG, each group having 12 rats. Meanwhile, immunohistochemistry (IMM) technique was used to investigate the expression of positive cell and integrated optical density (IOD) of metabotropic glutamate receptor 4 (mGluR4) and metabotropic glutamate receptor 5 (mGluR5), and the impact of exhaustive exercise played on oxidative stress indexes such as malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in ventrolateral thalamus of rats were also investigated in different groups. Results: Compared with CG, the expression of mGluR4 and mGluR5 protein of ventrolateral thalamus in 0EG and 24EG both significantly increased, and the value of mGluR4 in 48EG were still higher than control group, however the the value of mGluR5 in 48EG reduced to the rest level of control group. Meanwhile, the SOD activities of 0EG and 24EG group were significantly higher than the control group, and it was the same with GSH content in ventrolateral thalamus of rats. Meanwhile, MDA has been investigated that it increased significantly in 0EG and 24EG compared with control group, and the MDA level of 48EG was still significant higher than CG. Moreover, the indexes of muscle injury such as LD, CK and BUN all increased significantly post-exercise immediately and post-exercise 24 hours .Conclusion: Exercise fatigue could result in up-regulation of mGluR4 and mGluR5 and increace activity of SOD , GSH-PX and MDA in ventrolateral thalamus of rats, and it also induce the muscle injury by increase the level of LD, CK and BUN in serum, which suggested that ventrolateral thalamus was an important brain rigion to modulate the motor function, and mGluR4 and mGluR5 maybe two important receptors prevent from the increase of free radicals and muscle injury induced by exercise fatigue.

Reinforcement regulates timing variability in thalamus

Learning reduces variability but variability can facilitate learning. This paradoxical relationship has made it challenging to tease apart sources of variability that degrade performance from those that improve it. We tackled this question in a context-dependent timing task requiring humans and monkeys to flexibly produce different time intervals with different effectors. We identified two opposing factors contributing to timing variability: slow memory fluctuation that degrades performance and reward-dependent exploratory behavior that improves performance. Signatures of these opposing factors were evident across populations of neurons in the dorsomedial frontal cortex (DMFC), DMFC-projecting neurons in the ventrolateral thalamus, and putative target of DMFC in the caudate. However, only in the thalamus were the performance-optimizing regulation of variability aligned to the slow performance-degrading memory fluctuations. These findings reveal how variability caused by exploratory behavior might help to mitigate other undesirable sources of variability and highlight a potential role for thalamocortical projections in this process.

Contribution of the ventrolateral thalamus to the locomotion-related activity of motor cortex

How the activity of motor cortex is generated and the roles that different inputs to motor cortex play in formation of response properties of motor cortex neurons during movements remain unclear. This is the first study to characterize the contribution of the input from the ventrolateral thalamus (VL), the main subcortical input to motor cortex, to the activity of motor cortex neurons during vision-independent and vision-dependent locomotion.

Thalamic-Medial Temporal Lobe Connectivity Underpins Familiarity Memory

The neural basis of memory is highly distributed, but the thalamus is known to play a particularly critical role. However, exactly how the different thalamic nuclei contribute to different kinds of memory is unclear. Moreover, whether thalamic connectivity with the medial temporal lobe (MTL), arguably the most fundamental memory structure, is critical for memory remains unknown. We explore these questions using an fMRI recognition memory paradigm that taps familiarity and recollection (i.e., the two types of memory that support recognition) for objects, faces, and scenes. We show that the mediodorsal thalamus (MDt) plays a material-general role in familiarity, while the anterior thalamus plays a material-general role in recollection. Material-specific regions were found for scene familiarity (ventral posteromedial and pulvinar thalamic nuclei) and face familiarity (left ventrolateral thalamus). Critically, increased functional connectivity between the MDt and the parahippocampal (PHC) and perirhinal cortices (PRC) of the MTL underpinned increases in reported familiarity confidence. These findings suggest that familiarity signals are generated through the dynamic interaction of functionally connected MTL-thalamic structures.

Thalamic-medial temporal lobe connectivity underpins familiarity memory

The neural basis of memory is highly distributed, but the thalamus is known to play a particularly critical role. However, exactly how the different thalamic nuclei contribute to different kinds of memory is unclear. Moreover, whether thalamic connectivity with the medial temporal lobe (MTL), arguably the most fundamental memory structure, is critical for memory, remains unknown. We explore these questions using an fMRI recognition memory paradigm that taps familiarity and recollection (i.e., the two types of memory that support recognition) for objects, faces and scenes. We show that the mediodorsal thalamus (MDt) plays a material-general role in familiarity, while the anterior thalamus plays a material-general role in recollection. Material-specific regions were found for scene familiarity (ventral posteromedial and pulvinar thalamic nuclei) and face familiarity (left ventrolateral thalamus). Critically, increased functional connectivity between the MDt and the parahippocampal (PHC) and perirhinal cortices (PRC) of the MTL underpinned increases in reported familiarity confidence. These findings suggest that familiarity signals are generated through the dynamic interaction of functionally connected MTL-thalamic structures.

P.029 Limbic system involvement in absence seizures

Background: Absence epilepsy (AE) is believed to be generated by a thalamocortical network. Our laboratory showed that hippocampal neuronal firings were synchronous with the SWDs in the gamma butyrolactone (GBL) model of AE in rats. Here, we hypothesize that high frequency oscillations (HFOs) in the hippocampus and other parts of the limbic system were phase modulated by SWDs Methods: GBL (200 mg/kg i.p) was injected to induce SWDs in 6 male Long-Evans rats. Spontaneous local field potentials (LFPs) were recorded from electrodes implanted in the hippocampus and ventrolateral thalamus bilaterally and the right frontal cortex. For each LFP, modulation index (MI) gives the cross-frequency amplitude modulation of the HFOs (;90-250 Hz) by the phase of the SWD frequency at 2-8 Hz Results: Phase modulation of the HFOs by 2-8 Hz frequency increased for >45 min after GBL injection. MI increase was higher for hippocampal than thalamic LFPs, and not significant for frontal cortical LFP. MI for the nucleus accumbens LFP (N= 1 rat) also increased after GBL Conclusions: The modulation of HFOs (presumed local neural activity) by SWD frequency provides further support that the hippocampus and connected limbic system may become synchronous with the SWDs in AE

Approach to DBS in the Vicinity of the Ventral Intermediate Nucleus of the Thalamus DBS

The regional anatomy around the DBS lead in the ventral intermediate nucleus of the thalamus (Vim) determines efficacy and adverse effects. Understanding the regional anatomy allows the programmer to adjust the stimulation to provide optimal benefit and the absence of adverse effects. Vim is the target of therapeutic DBS. The ventrocaudal nucleus of the thalamus (Vc) lies posterior to the Vim. Electrical stimulation of Vc can cause treatment-limiting paresthesias. The corticospinal and cortical bulbar tracts in the internal capsule lie lateral and ventral to the Vim. Electrical stimulation of the internal capsule can cause tonic muscle contractions. There are multiple nomenclatures of the subnuclei of the thalamus. Although the term ventrolateral thalamus (VL) is commonly used in the physiology literature, ventral intermediate thalamus (Vim), is used in the DBS literature. Technically, the VL refers to both regions of the thalamus that receive inputs from GPi and cerebellum, whereas Vim refers to the cerebellar-receiving area of the thalamus and is thus a subdivision of the VL and is the target of DBS for tremor-related disorders.