scholarly journals Variation of connectivity across exemplar sensory and associative thalamocortical loops in the mouse

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Arghya Mukherjee ◽  
Navdeep Bajwa ◽  
Norman H Lam ◽  
César Porrero ◽  
Francisco Clasca ◽  
...  
Keyword(s):  
Structure Function ◽  
Functional Diversity ◽  
Functional Divergence ◽  
Structural Basis ◽  
Mediodorsal Thalamus ◽  
Associative Structure ◽  
Cortical Areas ◽  
Medial Geniculate ◽  
Cortical Excitation ◽  
Function Relationship

The thalamus engages in sensation, action, and cognition, but the structure underlying these functions is poorly understood. Thalamic innervation of associative cortex targets several interneuron types, modulating dynamics and influencing plasticity. Is this structure-function relationship distinct from that of sensory thalamocortical systems? Here, we systematically compared function and structure across a sensory and an associative thalamocortical loop in the mouse. Enhancing excitability of mediodorsal thalamus, an associative structure, resulted in prefrontal activity dominated by inhibition. Equivalent enhancement of medial geniculate excitability robustly drove auditory cortical excitation. Structurally, geniculate axons innervated excitatory cortical targets in a preferential manner and with larger synaptic terminals, providing a putative explanation for functional divergence. The two thalamic circuits also had distinct input patterns, with mediodorsal thalamus receiving innervation from a diverse set of cortical areas. Altogether, our findings contribute to the emerging view of functional diversity across thalamic microcircuits and its structural basis.

scholarly journals Structure-Function Relationship Studies on the Frog Skin Antimicrobial Peptide Tigerinin 1: Design of Analogs with Improved Activity and Their Action on Clinical Bacterial Isolates

2002 ◽  
Vol 46 (7) ◽  
pp. 2279-2283 ◽  
Author(s):  
Narasimhaiah Sitaram ◽  
Korrapati Purna Sai ◽  
Shashi Singh ◽  
Krishnan Sankaran ◽  
Ramakrishnan Nagaraj
Keyword(s):  
Antimicrobial Peptides ◽  
Structure Function ◽  
Disulfide Bridge ◽  
Structural Basis ◽  
Loop Structure ◽  
Disulfide Bridges ◽  
Bacterial Isolates ◽  
Optimal Activity ◽  
Function Relationship ◽  
Β Sheet

ABSTRACT Structure-function relationships in antimicrobial peptides have been extensively investigated in order to obtain improved analogs. Most of these studies have targeted either α-helical peptides or β-sheet peptides with multiple disulfide bridges. Tigerinins are short, nonhelical antimicrobial peptides with a single disulfide bridge. In this study, we have synthesized several analogs of tigerinin 1 with an aim to understand the structural basis of activity as well as improve its activity. The studies demonstrate that the loop structure of tigerinin 1 is essential for its optimal activity. However, linearization with increased cationic charges can compensate for loss of loop structure to some extent. Morphology of the cells after treatment with the active analogs shows extensive leakage of cytoplasmic contents. Tigerinin 1 and two of its analogs exhibit impressive activity against a variety of clinical bacterial isolates.

scholarly journals Competition and convergence between auditory and cross-modal visual inputs to primary auditory cortical areas

2011 ◽  
Vol 105 (4) ◽  
pp. 1558-1573 ◽  
Author(s):  
Yu-Ting Mao ◽  
Tian-Miao Hua ◽  
Sarah L. Pallas
Keyword(s):  
Auditory Cortex ◽  
Multisensory Processing ◽  
Sensory Deprivation ◽  
Target Space ◽  
Target Cells ◽  
Auditory Input ◽  
Visual Neurons ◽  
Cortical Areas ◽  
Visual Inputs ◽  
Medial Geniculate

Sensory neocortex is capable of considerable plasticity after sensory deprivation or damage to input pathways, especially early in development. Although plasticity can often be restorative, sometimes novel, ectopic inputs invade the affected cortical area. Invading inputs from other sensory modalities may compromise the original function or even take over, imposing a new function and preventing recovery. Using ferrets whose retinal axons were rerouted into auditory thalamus at birth, we were able to examine the effect of varying the degree of ectopic, cross-modal input on reorganization of developing auditory cortex. In particular, we assayed whether the invading visual inputs and the existing auditory inputs competed for or shared postsynaptic targets and whether the convergence of input modalities would induce multisensory processing. We demonstrate that although the cross-modal inputs create new visual neurons in auditory cortex, some auditory processing remains. The degree of damage to auditory input to the medial geniculate nucleus was directly related to the proportion of visual neurons in auditory cortex, suggesting that the visual and residual auditory inputs compete for cortical territory. Visual neurons were not segregated from auditory neurons but shared target space even on individual target cells, substantially increasing the proportion of multisensory neurons. Thus spatial convergence of visual and auditory input modalities may be sufficient to expand multisensory representations. Together these findings argue that early, patterned visual activity does not drive segregation of visual and auditory afferents and suggest that auditory function might be compromised by converging visual inputs. These results indicate possible ways in which multisensory cortical areas may form during development and evolution. They also suggest that rehabilitative strategies designed to promote recovery of function after sensory deprivation or damage need to take into account that sensory cortex may become substantially more multisensory after alteration of its input during development.

Mouse models to study von Willebrand factor structure-function relationships in vivo

2009 ◽  
Vol 29 (01) ◽  
pp. 17-20 ◽  
Author(s):  
I. Marx ◽  
I. Badirou ◽  
R. Pendu ◽  
O. Christophe ◽  
C. V. Denis
Keyword(s):  
Structure Function ◽  
Transient Expression ◽  
Von Willebrand Factor ◽  
Large Size ◽  
Mouse Hepatocytes ◽  
Function Relationship ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryVon Willebrand factor (VWF) structure-function relationship has been studied only through in vitro approaches. The VWF-deficient mouse model has been extremely useful to examine the in vivo function of VWF but does not allow a more subtle analysis of the relative importance of its different domains. However, considering the large size of VWF and its capacity to interact with various ligands in order to support platelet adhesion and aggregation, the necessity to evaluate independently these interactions appeared increasingly crucial. A recently developed technique, known as hydrodynamic injection, which allows transient expression of a transgene by mouse hepatocytes, proved very useful in this regard. Indeed, transient expression of various VWF mutants in VWF-deficient mice contributed to improve our knowledge about the role of VWF interaction with subendothelial collagens and with platelets receptors in VWF roles in haemostasis and thrombosis. These findings can provide new leads in the development of anti-thrombotic therapies.

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