Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease

The accumulation of amyloid-β in the brain is an essential feature of Alzheimer's disease. However, the impact of amyloid-β-accumulation on neuronal dysfunction on the single cell level in vivo is poorly understood. Here we investigate the progression of amyloid-β load in relation to neuronal dysfunction in the visual system of the APP23×PS45 mouse model of Alzheimer's disease. Using in vivo two-photon calcium imaging in the visual cortex, we demonstrate that a progressive deterioration of neuronal tuning for the orientation of visual stimuli occurs in parallel with the age-dependent increase of the amyloid-β load. Importantly, we find this deterioration only in neurons that are hyperactive during spontaneous activity. This impairment of visual cortical circuit function also correlates with pronounced deficits in visual-pattern discrimination. Together, our results identify distinct stages of decline in sensory cortical performance in vivo as a function of the increased amyloid-β-load

Complications after cryosurgery with new miniature cryoprobes in long hollow bones: An animal trial

BACKGROUND: In vitro studies show that new miniature cryoprobes are suitable for cryoablation of bone tissue. The aim of this animal trial on 24 sheep was to examine the perioperative complications, particularly the danger of embolism, of cryoablation when using miniature cryoprobes. METHODS: Cryoablations with 2 freeze-thaw cycles each were carried out in the epiphysis of the right tibia and the metaphysis of the left femur. Pulmonary artery pressure (PAP) and central venous pressure (CVP) were measured. Throughout the intra- and perioperative phase, heart rate and oxygen saturation by pulse oxymetry, blood gas and electrolytes were monitored regularly. Postoperative complications were examined up to 24 weeks postoperativ. RESULTS: As result, no significant increase of PAP, CVP or heart rate were observed. Blood gases were unremarkable, with pO(2 )and pCO(2 )remaining constant throughout the operation. Regarding pH, standard bicarbonate and base excess, only a non-significant shift towards a slight acidosis was seen. There was a mean hemoglobin decrease of 0.5 g/dl. One animal showed postoperative wound infection and wound edge necrosis. No major peri- and postoperative complications associated with cryosurgery of bone were observed, especially regarding clinically relevant pulmonary embolism. CONCLUSION: Surgery with new types of miniature cryoprobes appears to be a safe alternative to or a complement to conventional resection of abnormal bone tissue

Recovery of visual fields in brain-lesioned patients by reaction perimetry treatment

<p>Abstract</p> <p>Background</p> <p>The efficacy of treatment in hemianopic patients to restore missing vision is controversial. So far, successful techniques require laborious stimulus presentation or restrict improvements to selected visual field areas. Due to the large number of brain-damaged patients suffering from visual field defects, there is a need for an efficient automated treatment of the total visual field.</p> <p>Methods</p> <p>A customized treatment was developed for the reaction perimeter, permitting a time-saving adaptive-stimulus presentation under conditions of maximum attention. Twenty hemianopic patients, without visual neglect, were treated twice weekly for an average of 8.2 months starting 24.2 months after the insult. Each treatment session averaged 45 min in duration.</p> <p>Results</p> <p>In 17 out of 20 patients a significant and stable increase of the visual field size (average 11.3° ± 8.1) was observed as well as improvement of the detection rate in the defective visual field (average 18.6% ± 13.5). A two-factor cluster analysis demonstrated that binocular treatment was in general more effective in augmenting the visual detection rate than monocular. Four out of five patients with a visual field increase larger than 10° suffered from hemorrhage, whereas all seven patients with an increase of 5° or less suffered from infarction. Most patients reported that visual field restoration correlated with improvement of visual-related activities of daily living.</p> <p>Conclusion</p> <p>Rehabilitation treatment with the Lubeck Reaction Perimeter is a new and efficient method to restore part of the visual field in hemianopia. Since successful transfer of treatment effects to the occluded eye is achieved under monocular treatment conditions, it is hypothesized that the damaged visual cortex itself is the structure in which recovery takes place.</p

Feedforward and recurrent inhibitory receptive fields of principal cells in the cat’s dorsal lateral geniculate nucleus

Principal cells in the dorsal lateral geniculate nucleus receive both feedforward and recurrent inhibition. Despite many years of study, the receptive field structure of these inhibitory mechanisms has not been determined. Here, we have used intracellular recordings in vivo to differentiate between the two types of inhibition and map their respective receptive fields. The feedforward inhibition of a principal cell originates from the same type of retinal ganglion cells as its excitation, while the recurrent inhibition is provided by both on- and off-centre cells. Both inhibitory effects are strongest at the centre of the excitatory receptive field. The diameter of the feedforward inhibitory field is two times larger, and the recurrent two to four times larger than the excitatory field centre. The inhibitory circuitry is similar for X and Y principal cells

Slow GABAA mediated synaptic transmission in rat visual cortex

<p>Abstract</p> <p>Background</p> <p>Previous reports of inhibition in the neocortex suggest that inhibition is mediated predominantly through GABA_Areceptors exhibiting fast kinetics. Within the hippocampus, it has been shown that GABA_Aresponses can take the form of either fast or slow response kinetics. Our findings indicate, for the first time, that the neocortex displays synaptic responses with slow GABA_Areceptor mediated inhibitory postsynaptic currents (IPSCs). These IPSCs are kinetically and pharmacologically similar to responses found in the hippocampus, although the anatomical specificity of evoked responses is unique from hippocampus. Spontaneous slow GABA_AIPSCs were recorded from both pyramidal and inhibitory neurons in rat visual cortex.</p> <p>Results</p> <p>GABA_Aslow IPSCs were significantly different from fast responses with respect to rise times and decay time constants, but not amplitudes. Spontaneously occurring GABA_Aslow IPSCs were nearly 100 times less frequent than fast sIPSCs and both were completely abolished by the chloride channel blocker, picrotoxin. The GABA_Asubunit-specific antagonist, furosemide, depressed spontaneous and evoked GABA_Afast IPSCs, but not slow GABA_A-mediated IPSCs. Anatomical specificity was evident using minimal stimulation: IPSCs with slow kinetics were evoked predominantly through stimulation of layer 1/2 apical dendritic zones of layer 4 pyramidal neurons and across their basal dendrites, while GABA_Afast IPSCs were evoked through stimulation throughout the dendritic arborization. Many evoked IPSCs were also composed of a combination of fast and slow IPSC components.</p> <p>Conclusion</p> <p>GABA_Aslow IPSCs displayed durations that were approximately 4 fold longer than typical GABA_Afast IPSCs, but shorter than GABA_B-mediated inhibition. The anatomical and pharmacological specificity of evoked slow IPSCs suggests a unique origin of synaptic input. Incorporating GABA_Aslow IPSCs into computational models of cortical function will help improve our understanding of cortical information processing.</p

Cholinergic Activation of M2 Receptors Leads to Context-Dependent Modulation of Feedforward Inhibition in the Visual Thalamus

The temporal dynamics of inhibition within a neural network is a crucial determinant of information processing. Here, the authors describe in the visual thalamus how neuromodulation governs the magnitude and time course of inhibition in an input-dependent way

Neocortical Axon Arbors Trade-off Material and Conduction Delay Conservation

The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons. The morphology of individual axons, therefore, defines the course of information flow within the brain. More than a century ago, Ramón y Cajal proposed that conservation laws to save material (wire) length and limit conduction delay regulate the design of individual axon arbors in cerebral cortex. Yet the spatial and temporal communication costs of single neocortical axons remain undefined. Here, using reconstructions of in vivo labelled excitatory spiny cell and inhibitory basket cell intracortical axons combined with a variety of graph optimization algorithms, we empirically investigated Cajal's conservation laws in cerebral cortex for whole three-dimensional (3D) axon arbors, to our knowledge the first study of its kind. We found intracortical axons were significantly longer than optimal. The temporal cost of cortical axons was also suboptimal though far superior to wire-minimized arbors. We discovered that cortical axon branching appears to promote a low temporal dispersion of axonal latencies and a tight relationship between cortical distance and axonal latency. In addition, inhibitory basket cell axonal latencies may occur within a much narrower temporal window than excitatory spiny cell axons, which may help boost signal detection. Thus, to optimize neuronal network communication we find that a modest excess of axonal wire is traded-off to enhance arbor temporal economy and precision. Our results offer insight into the principles of brain organization and communication in and development of grey matter, where temporal precision is a crucial prerequisite for coincidence detection, synchronization and rapid network oscillations