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Rebecca A. Mease Patrik Krieger Alexander Groh 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(18):6798-6803
A major synaptic input to the thalamus originates from neurons in cortical layer 6 (L6); however, the function of this cortico–thalamic pathway during sensory processing is not well understood. In the mouse whisker system, we found that optogenetic stimulation of L6 in vivo results in a mixture of hyperpolarization and depolarization in the thalamic target neurons. The hyperpolarization was transient, and for longer L6 activation (>200 ms), thalamic neurons reached a depolarized resting membrane potential which affected key features of thalamic sensory processing. Most importantly, L6 stimulation reduced the adaptation of thalamic responses to repetitive whisker stimulation, thereby allowing thalamic neurons to relay higher frequencies of sensory input. Furthermore, L6 controlled the thalamic response mode by shifting thalamo–cortical transmission from bursting to single spiking. Analysis of intracellular sensory responses suggests that L6 impacts these thalamic properties by controlling the resting membrane potential and the availability of the transient calcium current IT, a hallmark of thalamic excitability. In summary, L6 input to the thalamus can shape both the overall gain and the temporal dynamics of sensory responses that reach the cortex.Sensory signals en route to the cortex undergo profound signal transformations in the thalamus. One important thalamic transformation is sensory adaptation. Adaptation is a common characteristic of sensory systems in which neural output adjusts to the statistics and dynamics of past stimuli, thereby better encoding small stimulus changes across a wide range of scales despite the limited range of possible neural outputs (1–3). Thalamic sensory adaptation is characterized by a steep decrease in action potential (AP) activity during sustained sensory stimulation (4–7), decreasing the efficacy at which subsequent sensory stimuli are transmitted to the cortex.The widely reported duality of thalamic response mode is another key property of thalamic information processing which further affects how sensory input reaches the cortex. In burst mode, sensory inputs are relayed as short, rapid clusters of APs; in contrast, in tonic mode the same inputs are translated into single APs. Both tonic and burst modes have been described during anesthesia/sleep and wakefulness/behavior, with a pronounced shift toward the tonic mode during alertness (8–12).Although the exact information content of thalamic bursts is not yet clear, it has been suggested that bursting may signal novel stimuli to the cortex, whereas the tonic mode enables linear encoding of fine stimulus details, e.g., when an object is examined (13, 14). One issue hampering the interpretation of burst/tonic responses is that currently it is unknown if the cortex itself is involved in the rapid changes in firing modes seen in the awake and anesthetized animal (15, 16) and which mechanisms initiate these shifts in vivo.On the biophysical level, the response mode depends on the resting membrane potential (RMP), which controls the availability of the transient low-threshold calcium current (IT) (17). Depolarization decreases the size of the IT-mediated low-threshold calcium spike (LTS), and fewer burst spikes are fired (18). Similarly, RMP influences adaptation in that depolarization reduces the voltage distance to the AP threshold, thereby increasing the probability that smaller, depressed inputs will trigger APs (6). Thus, the dynamics of the RMP may govern several key properties of signal transformation in the thalamus, thereby providing a common mechanism for controlling thalamic adaptation and response mode.Although subcortical inputs have been shown to influence thalamic firing modes (7, 9), we investigated the impact of cortical activity on thalamic sensory processing. Cortico–thalamic projections from cortical layer 6 (L6) are a likely candidate for regulating thalamic sensory processing with high spatial and temporal precision, because these projections provide a major input to the thalamus and, as shown by McCormick et al. (19), depolarize and modulate firing of thalamic cells in vitro.However, because of the inability to study sensory signals in brain slices, the role of L6 on thalamic input/output properties during sensory processing is not clear. Here, in the ventro posteromedial nucleus (VPM) of the mouse whisker thalamus, we investigate how L6 impacts the transmission of whisker inputs to the cortex. Recent advances in cell-type–specific approaches to dissect specific circuits in vivo (20–22) allowed us to activate the L6–thalamic pathway specifically and determine its impact on thalamic sensory processing.We found that cortical L6 can change key properties of thalamic sensory processing by controlling the interaction of intrinsic membrane properties and sensory inputs. This mechanism enables the cortex to control the frequency-dependent adaptation and the gain of its own input. 相似文献
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Fernanda Ortiz Pasi Aronen Petri K. Koskinen Raija K. Malmström Patrik Finne Eero O. Honkanen Harri Sintonen Risto P. Roine 《Transplant international》2014,27(11):1143-1151
The influence of dialysis modalities on HRQoL before and after kidney transplantation (KT) and the role of adherence to medication on HRQoL have not been fully studied. Sixty four dialysis patients who answered the 15D HRQoL survey during dialysis were surveyed again after KT. Adherence and employment were also investigated. The mean 15D score was highest among home hemodialysis patients (HHD) and lowest among in‐center hemodialysis patients (icHD). After KT, the mean 15D score improved significantly in 78.6% of peritoneal dialysis patients (PD), 47.6% of HHD, and 53.8% of icHD. Then, mean 15D score remained unchanged in 28.6% of HHD and in 23.1% of icHD patients. A deterioration in the 15D score occurred in 14.3% of PD, 23.1% of icHD, and 23.8% of HHD patients, and this was influenced by the number of pills (P = 0.04). Adherence to medication was the lowest in PD, timing being the most challenging task showing a connection to higher creatinine concentration (never forgot 1.41 mg/dl vs. forgot 2.08 mg/dl P = 0.05). Employed patients had a higher mean 15D score. The icHD and PD patients benefited the most from KT and HHD the least. Low pill burden and employment were linked to a better HRQoL. 相似文献
55.
Patrik Sundblad Roger Kölegård Ola Eiken 《European journal of applied physiology》2014,114(12):2521-2528
Purpose
Because leg arterial stiffness is higher in subjects with high G tolerance, we hypothesized that subjects with high G tolerance would have larger capacity for vasoconstriction.Methods
Sixteen subjects, eight with high and eight with low G tolerance (H and L group, respectively), were exposed to a cold pressor test (CPT) in supine and upright posture. Heart rate (HR), mean arterial pressure (MAP) and cardiac output (CO) were measured, and total peripheral resistance (TPR) and stroke volume (SV) were calculated.Results
In the supine position, CPT increased TPR more in the H group; 31 ± 18 % than in the L group; 11 ± 7 % (p < 0.05). The L group had larger increases in CO than the H group; 17 ± 16 vs. 3.4 ± 7 % (p = 0.06). In the upright position, the H group had a larger MAP response to CPT than the L group; 26 ± 14 vs. 14 ± 7 % (p = 0.06). The H group, but not the L group, had significant increases in TPR whereas the L group had significant increases in CO and SV.Conclusions
In response to CPT, the high G tolerance group elevated MAP by increasing TPR, whereas the low G tolerance group showed a dependency on increased CO. The H group seemed to have a larger vasoconstrictor reserve. The results further suggest that vasoconstrictor reserve capacity could constitute the link between the recent finding that indicates a relationship between G tolerance and arterial distensibility in the legs. 相似文献56.
Mats Martinell Tanja Andersson Steinar Smrholm Mannsverk Julia Bergholm Patrik Ellstrm Anna Hill Johan Lindh Rene Kaden 《Viruses》2022,14(3)
We describe a flight-associated infection scenario of seven individuals with a B.1.617.2 (Delta) lineage, harbouring an S:E484Q point mutation. In Sweden, at least 10% of all positive SARS-CoV-2 samples were sequenced in each county; the B.1.717.2 + S:E484Q combination was not detected in Sweden before and was imported within the scenario described in this report. The high transmission rate of the delta lineage combined with the S:E484Q mutation, associated with immune escape in other lineages, makes this specific genetic combination a possible threat to the global fight against the COVID-19 pandemic. Even within the Omicron wave, the B.1.617.2 + S:E484Q variant appeared in community samples in Sweden, as it seems that this combination has an evolutionary gain compared to other B.1.617.2 lineages. The here described genomic combination was not detectable with the common fasta file-based Pango-lineage analysis, hence increasing the probability of the true global prevalence to be higher. 相似文献
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Zarins Janis Aro Katri Bäck Leif Atula Timo Vuola Jyrki Lassus Patrik Keski-Säntti Harri 《European archives of oto-rhino-laryngology》2019,276(9):2577-2584
European Archives of Oto-Rhino-Laryngology - Surgical complications after total laryngopharyngectomy (TLP) are common, reconstruction is challenging, and patients often lose their ability to... 相似文献
60.
Patrik Gilje Olof Gidl?f Malin Rundgren Tobias Cronberg Mariam Al-Mashat Bj?rn Olde Hans Friberg David Erlinge 《Critical care (London, England)》2014,18(2):R40