Experience-Dependent Inhibitory Plasticity Is Mediated by CCK+ Basket Cells in the Developing Dentate Gyrus.

Early postnatal experience shapes both inhibitory and excitatory networks in the hippocampus. However, the underlying circuit plasticity is unclear. Using an enriched environment (EE) paradigm during the preweaning period in mice of either sex, we assessed the circuit plasticity of inhibitory cell types in the hippocampus. We found that cholecystokinin (CCK)-expressing basket cells strongly increased somatic inhibition on the excitatory granular cells (GCs) following EE, whereas another pivotal inhibitory cell type, parvalbumin (PV)-expressing cells, did not show changes. Using electrophysiological analysis and the use of cannabinoid receptor 1 (CB1R) agonist WIN 55 212-2, we demonstrate that the change in somatic inhibition from CCK+ neurons increases CB1R-mediated inhibition in the circuit. By inhibiting activity of the entorhinal cortex (EC) using a chemogenetic approach, we further demonstrate that the activity of the projections from the EC mediates the developmental assembly of CCK+ basket cell network. Altogether, our study places the experience-dependent remodeling of CCK+ basket cell innervation as a central process to adjust inhibition in the dentate gyrus and shows that cortical inputs to the hippocampus play an instructional role in controlling the refinement of the synaptic connections during the preweaning period.SIGNIFICANCE STATEMENT Brain plasticity is triggered by experience during postnatal brain development and shapes the maturing neural circuits. In humans, altered experience-dependent plasticity can have long-lasting detrimental effects on circuit function and lead to psychiatric disorders. Yet, the cellular mechanisms governing how early experience fine-tunes the maturing synaptic network is not fully understood. Here, taking advantage of an enrichment-housing paradigm, we unravel a new plasticity mechanism involved in the maintenance of the inhibitory to excitatory balance in the hippocampus. Our findings demonstrate that cortical activity instructs the assembly of the CCK+ basket cell network. Considering the importance of this specific cell type for learning and memory, experience-dependent remodeling of CCK+ cells may be a critical determinant for establishing appropriate neural networks.

Micromotion Analysis of Various Tibial Constructs in Moderate Tibial Defects in Revision Total Knee Arthroplasty.

BACKGROUND: The purpose of this study is to compare the micromotion of various tibial reconstruction strategies including short cemented and long cementless stems with or without metaphyseal augmentation. METHODS: A moderate tibial bone defect was milled into dual density polyurethane test blocks. Mechanical testing was performed on 4 test constructs: (1) short cemented stem (75-mm total length) alone; (2) short cemented stem with a symmetric metaphyseal cone; (3) a press-fit (175-mm total length) diaphyseal engaging tibial construct without a cone, and (4) the same press-fit tibial construct with a metaphyseal cone augment. Micromotion of the baseplate/cone construct with respect to the tibia block was measured during a stair descent loading profile for 10,000 cycles. The peak-to-peak micromotion of these various tibial constructs was compared. Unpaired t-tests were used to evaluate differences in peak-to-peak micromotion among the various tibial constructs tested. An analysis of variance was performed for final validation. RESULTS: The cemented short stem demonstrated similar varus/valgus displacement, internal/external rotation, compression, and lift-off micromotion values under loading compared to a cementless long stem. A tibial cone improved compression and lift-off micromotion for both cemented and cementless constructs. A short 50-mm cemented stem with a cone demonstrated a lower micromotion at the anterior SI location compared to a press-fit 150-mm cementless stem without a tibial cone. CONCLUSIONS: A short cemented tibial component with a cone achieved similar micromotion during simulated stair descent compared to a cementless diaphyseal press-fit implant in cases of moderate tibial defects.

Development and Verification of Novel Porous Titanium Metaphyseal Cones for Revision Total Knee Arthroplasty.

BACKGROUND: Porous metaphyseal cones are widely used in revision knee arthroplasty. A new system of porous titanium metaphyseal cones has been designed based on the femoral and tibial morphology derived from a computed tomography-based anatomical database. The purpose of this study is to evaluate the initial mechanical stability of the new porous titanium revision cone system by measuring the micromotion under physiologic loading compared with a widely-used existing porous tantalum metaphyseal cone system. METHODS: The new cones were designed to precisely fit the femoral and tibial anatomy, and 3D printing technology was used to manufacture these porous titanium cones. The stability of the new titanium cones and the widely-used tantalum cones were compared under physiologic loading conditions in bench top test model. RESULTS: The stability of the new titanium cones was either equivalent or better than the tantalum cones. The new titanium femoral cone construct had significantly less micromotion compared with the traditional femoral cone construct in 5 of the 12 directions measured (P < .05), whereas no statistical difference was found in 7 directions. The new porous titanium metaphyseal tibial cones demonstrated less micromotion in medial varus/valgus (P = .004) and posterior compressive micromotion (P = .002) compared with the traditional porous tantalum system. CONCLUSION: The findings of this biomechanical study demonstrate satisfactory mechanical stability of an anatomical-based porous titanium metaphyseal cone system for femoral and tibial bone loss as measured by micromotion under physiologic loading. The new cone design, in combination with instrumentation that facilitates surgical efficiency, is encouraging. Long-term clinical follow-up is warranted.