A neuroanatomical examination of embodied cognition: semantic generation to action-related stimuli

The theory of embodied cognition postulates that the brain represents semantic knowledge as a function of the interaction between the body and the environment. The goal of our research was to provide a neuroanatomical examination of embodied cognition using action-related pictures and words. We used functional magnetic resonance imaging (fMRI) to examine whether there were shared and/or unique regions of activation between an ecologically valid semantic generation task and a motor task in the parietal-frontocentral network (PFN), as a function of stimulus format (pictures versus words) for two stimulus types (hand and foot). Unlike other methods for neuroimaging analyses involving subtractive logic or conjoint analyses, this method first isolates shared and unique regions of activation within-participants before generating an averaged map. The results demonstrated shared activation between the semantic generation and motor tasks, which was organized somatotopically in the PFN, as well as unique activation for the semantic generation tasks in proximity to the hand or foot motor cortex. We also found unique and shared regions of activation in the PFN as a function of stimulus format (pictures versus words). These results further elucidate embodied cognition in that they show that brain regions activated during actual motor movements were also activated when an individual verbally generates action-related semantic information. Disembodied cognition theories and limitations are also discussed

Chronic maternal hyperglycemia induced during mid-pregnancy in rats increases RAGE expression, augments hippocampal excitability, and alters behavior of the offspring

Peer Reviewe

Investigating the role of LRRK2 in glutamate transmission and the implications for Parkinson’s disease pathophysiology

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder characterized by motor dysfunction and loss of dopamine neurons in the substantia nigra (SN). Increasing recognition of non-motor symptoms, many arising before clinical diagnosis and neuron death, has highlighted the involvement of other neurotransmitter systems in early disease processes. Mutations in LRRK2 present the most common cause of familial PD, and alter the function of the LRRK2 protein. Recent findings revealed that LRRK2 acts at synapses in multiple cell types, and may also be implicated in idiopathic PD. Investigating LRRK2’s role in non-dopaminergic neurotransmission may help identify early synaptic phenotypes and their contribution to PD pathophysiology, particularly within the basal ganglia. Perturbed neurotransmission converges on GABAergic spiny projection neurons (SPNs) in the striatum, which receive cortical and thalamic glutamatergic inputs, are modulated by dopamine from the SN, and form the gate to the basal ganglia. We examined the impact of altered excitatory input on SPN development and plasticity, by pharmacologically manipulating glutamatergic activity in corticostriatal cocultures from non-transgenic mice. We found that chronic action potential blockade reduced SPN dendritic spine density while increasing filopodia density, and altered presynaptic protein expression. While glycine stimulation in low magnesium was sufficient to drive spine density and AMPA receptor changes characteristic of long-term potentiation, mGluR activation by DHPG did not alter measures indicative of long-term depression. Thus, glutamatergic activity drives some bi-directional structural plasticity in SPNs, even in the absence of dopamine. Next, we examined how the most common LRRK2 mutation, the G2019S substitution, altered glutamatergic synapses. We used wild-type and LRRK2-G2019S knock-in (GKI) mice to compare synaptic transmission by electrophysiological recordings, and synaptic protein expression by immunocytochemistry. We found increased spontaneous glutamate release in cultured cortical neurons from GKI mice, and a synaptic reorganization in corticostriatal cocultures. Separately examining cortical and thalamic activity by optogenetic stimulation revealed altered evoked release in both input pathways in striatal slices from young GKI mice, with no changes in postsynaptic measures. Lastly, acute LRRK2 kinase inhibition restored neurotransmission in GKI slices; this confirms the pathogenic role of increased kinase activity and suggests its potential as a therapeutic target.Medicine, Faculty ofGraduat

Chronic lithium treatment alters the excitatory/inhibitory balance of synaptic networks and reduces mGluR5–PKC signalling in mouse cortical neurons

International audienceBackground: Bipolar disorder is characterized by cyclical alternation between mania and depression, often comorbid with psychosis and suicide. Compared with other medications, the mood stabilizer lithium is the most effective treatment for the prevention of manic and depressive episodes. However, the pathophysiology of bipolar disorder and lithium’s mode of action are yet to be fully understood. Evidence suggests a change in the balance of excitatory and inhibitory activity, favouring excitation in bipolar disorder. In the present study, we sought to establish a holistic understanding of the neuronal consequences of lithium exposure in mouse cortical neurons, and to identify underlying mechanisms of action.Methods: We used a range of technical approaches to determine the effects of acute and chronic lithium treatment on mature mouse cortical neurons. We combined RNA screening and biochemical and electrophysiological approaches with confocal immunofluorescence and live-cell calcium imaging.Results: We found that only chronic lithium treatment significantly reduced intracellular calcium flux, specifically by activating metabotropic glutamatergic receptor 5. This was associated with altered phosphorylation of protein kinase C and glycogen synthase kinase 3, reduced neuronal excitability and several alterations to synapse function. Consequently, lithium treatment shifts the excitatory–inhibitory balance toward inhibition.Limitations: The mechanisms we identified should be validated in future by similar experiments in whole animals and human neurons.Conclusion: Together, the results revealed how lithium dampens neuronal excitability and the activity of the glutamatergic network, both of which are predicted to be overactive in the manic phase of bipolar disorder. Our working model of lithium action enables the development of targeted strategies to restore the balance of overactive networks, mimicking the therapeutic benefits of lithium but with reduced toxicity