Raising cytosolic Cl- in cerebellar granule cells affects their excitability and vestibulo-ocular learning.

Cerebellar cortical throughput involved in motor control comprises granule cells (GCs) and Purkinje cells (PCs), both of which receive inhibitory GABAergic input from interneurons. The GABAergic input to PCs is essential for learning and consolidation of the vestibulo-ocular reflex, but the role of GC excitability remains unclear. We now disrupted the Kcc2 K-Cl cotransporter specifically in either cell type to manipulate their excitability and inhibition by GABA(A)-receptor Cl(-) channels. Although Kcc2 may have a morphogenic role in synapse development, Kcc2 disruption neither changed synapse density nor spine morphology. In both GCs and PCs, disruption of Kcc2, but not Kcc3, increased [Cl(-)](i) roughly two-fold. The reduced Cl(-) gradient nearly abolished GABA-induced hyperpolarization in PCs, but in GCs it merely affected excitability by membrane depolarization. Ablation of Kcc2 from GCs impaired consolidation of long-term phase learning of the vestibulo-ocular reflex, whereas baseline performance, short-term gain-decrease learning and gain consolidation remained intact. These functions, however, were affected by disruption of Kcc2 in PCs. GC excitability plays a previously unknown, but specific role in consolidation of phase learning.

Efficacy and safety of a collagen matrix for cranial and spinal dural reconstruction using different fixation techniques.

OBJECT: The use of dural grafts is frequently unavoidable when tension-free dural closure cannot be achieved following neurosurgical procedures or trauma. Biodegradable collagen matrices serve as a scaffold for the regrowth of natural tissue and require no suturing. The aim of this study was to investigate the efficacy and safety of dural repair with a collagen matrix using different fixation techniques. METHODS: A total of 221 patients (98 male and 123 female; mean age 55.6 +/- 17.8 years) undergoing cranial (86.4%) or spinal (13.6%) procedures with the use of a collagen matrix dural graft were included in this retrospective study. The indications for use, fixation techniques, and associated complications were recorded. RESULTS: There were no complications of the dural graft in spinal use. Five (2.6%) of 191 patients undergoing cranial procedures developed infections, 3 of which (1.6%) were deep infections requiring surgical revision. There was no statistically significant relationship between the operative field status before surgery and the occurrence of a postoperative wound infection (p = 0.684). In the 191 patients undergoing a cranial procedure, cerebrospinal fluid (CSF) collection occurred in 5 patients (2.6%) and a CSF fistula in 5 (2.6%), 3 of whom (1.6%) required surgical revision. No patient who underwent an operation with preexisting CSF leakage had postoperative CSF leakage. Postoperative infection significantly increased the risk for postoperative CSF leakage. The collagen matrix was used without additional fixation in 124 patients (56.1%), with single fixation in 55 (24.9%), and with multiple fixations in 42 (19%). There were no systemic allergic reactions or local skin changes. Follow-up imaging in 112 patients (50.7%) revealed no evidence of any adverse reaction to the collagen graft. CONCLUSIONS: The collagen matrix is an effective and safe cranial and spinal dural substitute that can be used even in cases of an existing local infection. Postoperative deep infection increases the risk for CSF leakage.

Arabidopsis fhl/fhy1 double mutant reveals a distinct cytoplasmic action of phytochrome A.

Phytochrome A (phyA) plays an important role during germination and early seedling development. Because phyA is the primary photoreceptor for the high-irradiance response and the very-low-fluence response, it can trigger development not only in red and far-red (FR) light but also in a wider range of light qualities. Although phyA action is generally associated with translocation to the nucleus and regulation of transcription, there is evidence for additional cytoplasmic functions. Because nuclear accumulation of phyA has been shown to depend on far-red-elongated hypocotyl 1 (FHY1) and FHL (FHY1-like), investigation of phyA function in a double fhl/fhy1 mutant might be valuable in revealing the mechanism of phyA translocation and possible cytoplasmic functions. In fhl/fhy1, the FR-triggered nuclear translocation of phyA could no longer be detected but could be restored by transgenic expression of CFP:FHY1. Whereas the fhl/fhy1 mutant showed a phyA phenotype in respect to hypocotyl elongation and cotyledon opening under high-irradiance response conditions as well as a typical phyA germination phenotype under very-low-fluence response conditions, fhl/fhy1 showed no phenotype with respect to the phyA-dependent abrogation of negative gravitropism in blue light and in red-enhanced phototropism, demonstrating clear cytoplasmic functions of phyA. Disturbance of phyA nuclear import in fhl/fhy1 led to formation of FR-induced phyA:GFP cytoplasmic foci resembling the sequestered areas of phytochrome. FHY1 and FHL play crucial roles in phyA nuclear translocation and signaling. Thus the double-mutant fhl/fhy1 allows nuclear and cytoplasmic phyA functions to be separated, leading to the novel identification of cytoplasmic phyA responses.