Monocular deprivation evokes a prominent shift of neuronal responses in the visual cortex toward the open eye, accompanied by functional and structural synaptic rearrangements. This shift is ...reversible, but it is unknown whether the recovery happens at the level of individual neurons or whether it reflects a population effect. We used ratiometric Ca²⁺ imaging to follow the activity of the same excitatory layer 2/3 neurons in the mouse visual cortex over months during repeated episodes of ocular dominance (OD) plasticity. We observed robust shifts toward the open eye in most neurons. Nevertheless, these cells faithfully returned to their predeprivation OD during binocular recovery. Moreover, the initial network correlation structure was largely recovered, suggesting that functional connectivity may be regained despite prominent experience-dependent plasticity.
The brain extracts behaviourally relevant sensory input to produce appropriate motor output. On the one hand, our constantly changing environment requires this transformation to be plastic. On the ...other hand, plasticity is thought to be balanced by mechanisms ensuring constancy of neuronal representations in order to achieve stable behavioural performance. Yet, prominent changes in synaptic strength and connectivity also occur during normal sensory experience, indicating a certain degree of constitutive plasticity. This raises the question of how stable neuronal representations are on the population level and also on the single neuron level. Here, we review recent data from longitudinal electrophysiological and optical recordings of single-cell activity that assess the long-term stability of neuronal stimulus selectivities under conditions of constant sensory experience, during learning, and after reversible modification of sensory input. The emerging picture is that neuronal representations are stabilized by behavioural relevance and that the degree of long-term tuning stability and perturbation resistance directly relates to the functional role of the respective neurons, cell types and circuits. Using a ‘toy’ model, we show that stable baseline representations and precise recovery from perturbations in visual cortex could arise from a ‘backbone’ of strong recurrent connectivity between similarly tuned cells together with a small number of ‘anchor’ neurons exempt from plastic changes.
This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.
We summarize here the results presented and subsequent discussion from the meeting on Integrating Hebbian and Homeostatic Plasticity at the Royal Society in April 2016. We first outline the major ...themes and results presented at the meeting. We next provide a synopsis of the outstanding questions that emerged from the discussion at the end of the meeting and finally suggest potential directions of research that we believe are most promising to develop an understanding of how these two forms of plasticity interact to facilitate functional changes in the brain.
This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.
Background
Anastomotic leakage after esophagectomy is a life-threatening complication. No comparative outcome analyses for the different treatment regimens are yet available.
Methods
In a ...single-center study, data from all esophagectomy patients from January 1995 to January 2012, including tumor characteristics, surgical procedure, postoperative anastomotic leakage, leakage therapy regimens, APACHE II scores, and mortality, were collected, and predictors of patient survival after anastomotic leakage were analyzed.
Results
Among 366 resected patients, 62 patients (16 %) developed an anastomotic leak, 16 (26 %) of whom died. Therapy regimens included surgical revision (
n
= 18), endoscopic endoluminal vacuum therapy (
n
= 17), endoscopic stent application (
n
= 12), and conservative management (
n
= 15). APACHE II score at the initiation of treatment for leakage was the strongest predictor of in-hospital mortality (
p
< 0.0017). Conservatively managed patients showed mild systemic illness (mean APACHE II score 5) and no mortality. In systemically ill patients matched for APACHE II scores (mean, 14.4), endoscopic endoluminal vacuum therapy patients had lower mortality (12 %) compared to surgically treated (50 %,
p
= 0.01) cases and patients managed by stent placement (83 %,
p
= 00014, log rank test). No other clinical or laboratory parameters significantly influenced patient survival.
Conclusions
Endoscopic endoluminal vacuum therapy was the best treatment of anastomotic leakage in systemically ill patients after esophagectomy in this retrospective analysis. It should therefore be considered an important instrument in the management of this disorder.
Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by abnormal social interactions, communication deficits and stereotyped or repetitive behaviors. ...Although the etiology of ASD remains elusive, converging lines of research indicate that mitochondrial dysfunction may play a substantive role in disease pathophysiology. Without an established causal link, the generation of therapeutic targets for ASD has been relatively unsuccessful and has focused solely on individual symptoms. The ketogenic diet (KD) is a high-fat low-carbohydrate diet that has previously been used for the treatment of intractable epilepsy and is known to enhance mitochondrial function. The purpose of this study was to determine if the KD could reverse the social deficits and mitochondrial dysfunction identified in the prenatal valproic acid (VPA) rodent model of ASD. Sprague-Dawley dams were administered VPA or saline on gestational day 12.5. The pups were treated with the KD or their standard diet (SD) for 10 days beginning on postnatal day 21 (PD21). On PD35 juvenile play behavior was tested with the play-fighting paradigm and rats were then sacrificed for mitochondrial bioenergetic analysis. The offspring exposed to VPA prenatally demonstrated a significant decrease in the number of play initiations/attacks and this was reversed with the KD. Prenatal VPA exposure also disrupted the pattern of play responses; VPA/SD animals used complete rotations more often than saline control animals. Treatment with the KD did not affect the number of complete rotations. In addition, while prenatal exposure to VPA altered mitochondrial respiration, the KD was able to restore aspects of bioenergetic dysfunction. As the KD was able to modify complex social behaviors and mitochondrial respiration, it may be a useful treatment option for ASD. Future studies will need to examine the effectiveness of the KD to reverse the two additional core deficits of ASD and to explore various treatment regimens to determine optimal treatment duration and formulation.
Experience-dependent plasticity in the visual system is traditionally thought to be exclusively cortical whereas the dorsal lateral geniculate nucleus (dLGN) is classically considered to just be a ...‘relay’ of visual information between the retina and the cortex. However, a number of recent experiments call into question the simplistic view of visual cortex being the only site of plasticity. Thalamic neurons, at least in mouse dLGN, combine inputs from ganglion cells located in both eyes and recent evidence suggests that the feature selectivity of dLGN neurons is subject to experience-dependent plasticity. Here we discuss new insights into the nature of thalamic visual processing, focusing on the unexpected degree and plasticity of functional binocular convergence in mouse dLGN.
GABA B receptors are the G-protein–coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. GABA B receptors are abundant on dendritic spines, where they dampen postsynaptic ...excitability and inhibit Ca 2+ influx through NMDA receptors when activated by spillover of GABA from neighboring GABAergic terminals. Here, we show that an excitatory signaling cascade enables spines to counteract this GABA B -mediated inhibition. We found that NMDA application to cultured hippocampal neurons promotes dynamin-dependent endocytosis of GABA B receptors. NMDA-dependent internalization of GABA B receptors requires activation of Ca 2+ /Calmodulin-dependent protein kinase II (CaMKII), which associates with GABA B receptors in vivo and phosphorylates serine 867 (S867) in the intracellular C terminus of the GABA B1 subunit. Blockade of either CaMKII or phosphorylation of S867 renders GABA B receptors refractory to NMDA-mediated internalization. Time-lapse two-photon imaging of organotypic hippocampal slices reveals that activation of NMDA receptors removes GABA B receptors within minutes from the surface of dendritic spines and shafts. NMDA-dependent S867 phosphorylation and internalization is predominantly detectable with the GABA B1b subunit isoform, which is the isoform that clusters with inhibitory effector K + channels in the spines. Consistent with this, NMDA receptor activation in neurons impairs the ability of GABA B receptors to activate K + channels. Thus, our data support that NMDA receptor activity endocytoses postsynaptic GABA B receptors through CaMKII-mediated phosphorylation of S867. This provides a means to spare NMDA receptors at individual glutamatergic synapses from reciprocal inhibition through GABA B receptors.
The response of individual neurons to stable sensory input or behavioral output can change over time. A new study provides evidence from the mouse visual system that such drift does not follow the ...hierarchy of information flow across the brain.
The response of individual neurons to stable sensory input or behavioral output can change over time. A new study provides evidence from the mouse visual system that such drift does not follow the hierarchy of information flow across the brain.
The Goto Kakizaki (GK) rat is a widely used animal model to study defective glucose-stimulated insulin release in type-2 diabetes (T2D). As in T2D patients, the expression of several proteins ...involved in Ca(2+)-dependent exocytosis of insulin-containing large dense-core vesicles is dysregulated in this model. So far, a defect in late steps of insulin secretion could not be demonstrated. To resolve this apparent contradiction, we studied Ca(2+)-secretion coupling of healthy and GK rat beta cells in acute pancreatic tissue slices by assessing exocytosis with high time-resolution membrane capacitance measurements. We found that beta cells of GK rats respond to glucose stimulation with a normal increase in the cytosolic Ca(2+) concentration. During trains of depolarizing pulses, the secretory activity from GK rat beta cells was defective in spite of upregulated cell size and doubled voltage-activated Ca(2+) currents. In GK rat beta cells, evoked Ca(2+) entry was significantly less efficient in triggering release than in nondiabetic controls. This impairment was neither due to a decrease of functional vesicle pool sizes nor due to different kinetics of pool refilling. Strong stimulation with two successive trains of depolarizing pulses led to a prominent activity-dependent facilitation of release in GK rat beta cells, whereas secretion in controls was unaffected. Broad-spectrum inhibition of PKC sensitized Ca(2+)-dependent exocytosis, whereas it prevented the activity-dependent facilitation in GK rat beta cells. We conclude that a decrease in the sensitivity of the GK rat beta-cell to depolarization-evoked Ca(2+) influx is involved in defective glucose-stimulated insulin secretion. Furthermore, we discuss a role for constitutively increased activity of one or more PKC isoenzymes in diabetic rat beta cells.
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