Encoding and retrieval in a CA1 microcircuit model of the hippocampus

Recent years have witnessed a dramatic accumulation of knowledge about the morphological, physiological and molecular characteristics, as well as connectivity and synaptic properties of neurons in the mammalian hippocampus. Despite these advances, very little insight has been gained into the computational function of the different neuronal classes; in particular, the role of the various inhibitory interneurons in encoding and retrieval of information remains elusive. Mathematical and computational models of microcircuits play an instrumental role in exploring microcircuit functions and facilitate the dissection of operations performed by diverse inhibitory interneurons. A model of the CA1 microcircuitry is presented using biophysical representations of its major cell types: pyramidal, basket, axo-axonic, bistratified and oriens lacunosummoleculare cells. Computer simulations explore the biophysical mechanisms by which encoding and retrieval of spatio-temporal input patterns are achieved by the CA1 microcircuitry. The model proposes functional roles for the different classes of inhibitory interneurons in the encoding and retrieval cycles

Development of a planar multi-body model of the human knee joint

The aim of this work is to develop a dynamic model for the biological human knee joint. The model is formulated in the framework of multibody systems methodologies, as a system of two bodies, the femur and the tibia. For the purpose of describing the formulation, the relative motion of the tibia with respect to the femur is considered. Due to their higher stiffness compared to that of the articular cartilages, the femur and tibia are considered as rigid bodies. The femur and tibia cartilages are considered to be deformable structures with specific material characteristics. The rotation and gliding motions of the tibia relative to the femur can not be modeled with any conventional kinematic joint, but rather in terms of the action of the knee ligaments and potential contact between the bones. Based on medical imaging techniques, the femur and tibia profiles in the sagittal plane are extracted and used to define the interface geometric conditions for contact. When a contact is detected, a continuous non-linear contact force law is applied which calculates the contact forces developed at the interface as a function of the relative indentation between the two bodies. The four basic cruciate and collateral ligaments present in the knee are also taken into account in the proposed knee joint model, which are modeled as non-linear elastic springs. The forces produced in the ligaments, together with the contact forces, are introduced into the system’s equations of motion as external forces. In addition, an external force is applied on the center of mass of the tibia, in order to actuate the system mimicking a normal gait motion. Finally, numerical results obtained from computational simulations are used to address the assumptions and procedures adopted in this study.Fundação para a Ciência e a Tecnologia (FCT

Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy

<p>Abstract</p> <p>Background</p> <p>Diverse Mouse genetic models of neurodevelopmental, neuropsychiatric, and neurodegenerative causes of impaired cognition exhibit at least four convergent points of synaptic malfunction: 1) Strength of long-term potentiation (LTP), 2) Strength of long-term depression (LTD), 3) Relative inhibition levels (Inhibition), and 4) Excitatory connectivity levels (Connectivity).</p> <p>Results</p> <p>To test the hypothesis that pathological increases or decreases in these synaptic properties could underlie imbalances at the level of basic neural network function, we explored each type of malfunction in a simulation of autoassociative memory. These network simulations revealed that one impact of impairments or excesses in each of these synaptic properties is to shift the trade-off between pattern separation and pattern completion performance during memory storage and recall. Each type of synaptic pathology either pushed the network balance towards intolerable error in pattern separation or intolerable error in pattern completion. Imbalances caused by pathological impairments or excesses in LTP, LTD, inhibition, or connectivity, could all be exacerbated, or rescued, by the simultaneous modulation of any of the other three synaptic properties.</p> <p>Conclusions</p> <p>Because appropriate modulation of any of the synaptic properties could help re-balance network function, regardless of the origins of the imbalance, we propose a new strategy of personalized cognitive therapeutics guided by assay of pattern completion vs. pattern separation function. Simulated examples and testable predictions of this theorized approach to cognitive therapeutics are presented.</p

The effect of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial: a meta-analysis of the US, German, Netherlands, and Belgium sub-studies

PURPOSE: We performed a meta-analysis of three sub-studies of the randomized Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial to determine the effects of exemestane and tamoxifen on bone health. METHODS: Patients received exemestane or tamoxifen as adjuvant therapy for hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed at baseline and after 12 and 24 months of treatment. Bone turnover markers were also measured. RESULTS: Patients receiving tamoxifen showed a mean increase from baseline in lumbar spine BMD of 1.2% at month 12 and 0.2% at month 24. Patients receiving exemestane showed a mean decrease from baseline of 2.6% after 12 months and 3.5% after 24 months. There were significant differences in the changes in lumbar spine BMD between treatment groups (P < 0.0001 at both time points). Changes in BMD from baseline at the total hip were also significantly different between exemestane and tamoxifen (P < 0.05 at both time points). Bone turnover markers decreased from baseline with tamoxifen and increased with exemestane. CONCLUSIONS: Exemestane resulted in decreases in BMD and increases in bone turnover markers. BMD increased and bone turnover markers decreased with tamoxifen.Experimentele farmacotherapi