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PubMed1992

[Thermal distribution in the agar phantom by a new intracavitary RF applicator for prostate gland].

Some studies suggest that the prostate gland is one of the most difficult portions of the body to heat up even by radio frequency (RF) capacitive heating, which is well established as a useful means for deep regional hyperthermia because of its non-uniform power absorption. We have developed a new type of intracavitary applicator for RF capacitive heating which can be connected to an 8 MHz RF heating device (Thermotron-RF8). The applicator is a balloon-type catheter which is filled with electrolyte, such as physiological saline, 3% saline or 3% ferrous sulfate solution, and then put between a pair of regular RF capacitive heating electrodes. The heating characteristics of the applicator were examined by using an agar phantom that is electrically equivalent to muscles. When the applicator was connected to the electrode of the RF generator with a copper cord, the balloon filled with electrolyte operated as an inner electrode. The effective hot area around the balloon of the catheter was observed, and the size of the hot area was changed by the kinds of electrolytes used and their concentration. With this adaptive technique, it is possible to maintain an adequate thermal distribution at a tumor in the uterus, urinary bladder and rectum, as well as the prostate gland.

Agar↗

PubMed2004

Structural basis for the carbohydrate specificities of artocarpin: variation in the length of a loop as a strategy for generating ligand specificity.

Artocarpin, a tetrameric lectin of molecular mass 65 kDa, is one of the two lectins extracted from the seeds of jackfruit. The structures of the complexes of artocarpin with mannotriose and mannopentose reported here, together with the structures of artocarpin and its complex with Me-alpha-mannose reported earlier, show that the lectin possesses a deep-seated binding site formed by three loops. The binding site can be considered as composed of two subsites; the primary site and the secondary site. Interactions at the primary site composed of two of the loops involve mainly hydrogen bonds, while those at the secondary site comprising the third loop are primarily van der Waals in nature. Mannotriose in its complex with the lectin interacts through all the three mannopyranosyl residues; mannopentose interacts with the protein using at least three of the five mannose residues. The complexes provide a structural explanation for the carbohydrate specificities of artocarpin. A detailed comparison with the sugar complexes of heltuba, the only other mannose-specific jacalin-like lectin with known three-dimensional structure in sugar-bound form, establishes the role of the sugar-binding loop constituting the secondary site, in conferring different specificities at the oligosaccharide level. This loop is four residues longer in artocarpin than in heltuba, providing an instance where variation in loop length is used as a strategy for generating carbohydrate specificity.

Binding Sites↗

PubMed2006

Validation of a randomization procedure to assess animal habitat preferences: microhabitat use of tiger sharks in a seagrass ecosystem.

1. Tiger sharks Galeocerdo cuvier are important predators in a variety of nearshore communities, including the seagrass ecosystem of Shark Bay, Western Australia. Because tiger sharks are known to influence spatial distributions of multiple prey species, it is important to understand how they use habitats at a variety of spatial scales. We used a combination of catch rates and acoustic tracking to determine tiger shark microhabitat use in Shark Bay. 2. Comparing habitat-use data from tracking against the null hypothesis of no habitat preference is hindered in Shark Bay, as elsewhere, by the difficulty of defining expected habitat use given random movement. We used randomization procedures to generate expected habitat use in the absence of habitat preference and expected habitat use differences among groups (e.g. males and females). We tested the performance of these protocols using simulated data sets with known habitat preferences. 3. The technique correctly classified sets of simulated tracks as displaying a preference or not and was a conservative test for differences in habitat preferences between subgroups of tracks (e.g. males vs. females). 4. Sharks preferred shallow habitats over deep ones, and preferred shallow edge microhabitats over shallow interior ones. The use of shallow edges likely increases encounter rates with potential prey and may have profound consequences for the dynamics of Shark Bay's seagrass ecosystem through indirect effects transmitted by grazers that are common prey of tiger sharks. 5. Females showed a greater tendency to use shallow edge microhabitats than did males; this pattern was not detected by traditional analysis techniques. 6. The randomization procedures presented here are applicable to many field studies that use tracking by allowing researchers both to determine overall habitat preferences and to identify differences in habitat use between groups within their sample.

Animals↗

PubMed1998

Formation of an amino-acid-binding pocket through adaptive zippering-up of a large DNA hairpin loop.

BACKGROUND: In vitro selection has identified DNA aptamers that target cofactors, amino acids, peptides and proteins. Structure determination of such ligand-DNA aptamer complexes should elucidate the details of adaptive DNA structural transitions, binding-pocket architectures and ligand recognition. We have determined the solution structure of the complex of a DNA aptamer containing a guanine-rich 18-residue hairpin loop that binds L-argininamide with approximately 100 microM affinity. RESULTS: The DNA aptamer generates its L-argininamide-binding pocket by adaptive zippering up the 18-residue loop through formation of Watson-Crick pairs, mismatch pairs and base triples, while maximizing stacking interactions. Three of the four base triples involve minor-groove recognition through sheared G.A mismatch formation. The unique fold is also achieved through positioning of an adenine residue deep within the minor groove and through nestling of a smaller loop within the larger loop on complex formation. The accessibility to the unique L-argininamide-binding pocket is restricted by a base pair that bridges across one side of the major-groove-binding site. The guanidinium group of the bound L-argininamide aligns through intermolecular hydrogen-bond formation with the base edges of nonadjacent guanine and cytosine residues while being sandwiched between the planes of nonadjacent guanine residues. CONCLUSIONS: The available structures of L-arginine/L-argininamide bound to their DNA and RNA targets define the common principles and patterns associated with molecular recognition, as well as the diversity of intermolecular hydrogen-bonding alignments associated with the distinct binding pockets.

Amino Acids↗

PubMed2002

Comparative neuroethology of feeding control in molluscs.

Over the last 30 years, many laboratories have examined, in parallel, the feeding behaviour of gastropod molluscs and the properties of the nervous system that give rise to this behaviour. Equal attention to both behavioural and neurobiological issues has provided deep insight into the functioning of the nervous system in generating and controlling behaviour. The conclusions derived from studies on gastropod feeding are generally consistent with those from other systems, but often provide more detailed information on the behavioural function of a particular property of the nervous system. A review of the literature on gastropod feeding illustrates a number of important messages. (i) Many of the herbivorous gastropods display similarities in behaviour that are reflected in corresponding similarities in neural anatomy, pharmacology and physiology. By contrast, the same aspects of the behaviour of different carnivorous species are quite variable, possibly because of their specialised prey-capture techniques. Nonetheless, some aspects of the neural control of feeding are preserved. (ii) Feeding in all species is flexible, with the behaviour and the physiology adapting to changes in the current environment and internal state and as a result of past experience. Flexibility arises via processes that may take place at many neural sites, and much of the modulation underlying behavioural flexibility is understood at a systems and at a cellular level. (iii) Neurones seem to have specific functions that are consistent with their endogenous properties and their synaptic connections, suggesting that individual neurones code specific pieces of information (i.e. they are 'grandmother cells'). However, the properties of a neurone can be extremely complex and can be understood only in the context of the complete neural circuit and the behaviour that it controls. In systems that are orders of magnitude more complex, it would be impossible to understand the functional properties of an individual neurone, even if it also coded specific information. (iv) Systems such as gastropod feeding may provide a model for understanding the functional properties of more complex systems.

Animals↗

PubMed2005

Molecular recognition mechanisms of thrombin.

Thrombin is the final protease generated in the blood coagulation cascade, and is the only factor capable of cleaving fibrinogen to create a fibrin clot. Unlike every other coagulation protease, thrombin is composed solely of its serine protease domain, so that once formed it can diffuse freely to encounter a large number of potential substrates. Thus thrombin serves many functions in hemostasis through the specific cleavage of at least a dozen substrates. The solution of the crystal structure of thrombin some 15 years ago revealed a deep active site cleft and two adjacent basic exosites, and it was clear that thrombin must utilize these unique features in recognizing its substrates. Just how this occurs is still being investigated, but recent data from thrombin mutant libraries and crystal structures combine to paint the clearest picture to date of the molecular determinants of substrate recognition by thrombin. In almost all cases, both thrombin exosites are involved, either through direct interaction with the substrate protein or through indirect interaction with a third cofactor molecule. The purpose of this article is to summarize recent biochemical and structural data in order to provide insight into the thrombin molecular recognition events at the heart of hemostasis.

Animals↗

PubMed1995

Control of the necrosed tissue volume during noninvasive ultrasound surgery using a 16-element phased array.

Focused high-power ultrasound beams are well suited for noninvasive local destruction of deep target volumes. In order to avoid cavitation and to utilize only thermal tissue damage, high frequencies (1-5 MHz) are used in ultrasonic surgery. However, the focal spots generated by sharply focused transducers become so small that only small tumors can be treated in a reasonable time. Phased array ultrasound transducers can be employed to electronically scan a focal spot or to produce multiple foci in the desired region to increase the treated volume. In this article, theoretical and experimental studies of spherically curved square-element phased arrays for use in ultrasonic surgery were performed. The simulation results were compared with experimental results from a 16-element array. It was shown that the phased array could control the necrosed tissue volume by using closely spaced multiple foci. The phased array can also be used to enlarge a necrosed tissue volume in only one direction at a time, i.e., lateral or longitudinal. The spherically curved 16 square-element phased array can produce useful results by varying the phase and amplitude setting. Four focal points can be easily generated with a distance of two or four wavelengths between the two closest peaks. The maximum necrosed tissue volume generated by the array can be up to sixteen times the volume induced by a similar spherical transducer. Therefore the treatment time could be reduced compared with single transducer treatment.

Biophysical Phenomena↗

PubMed1989

Soft-tissue effects of biliary extracorporeal shockwave lithotripsy in swine.

This study investigates the soft-tissue effects of biliary extracorporeal shockwave lithotripsy (BESWL) using a recently developed lithotripter, which consists of an electromagnetic shockwave generator and an integrated ultrasonic targeting system. Sixteen swine, evenly divided into four groups, underwent BESWL. One group had one BESWL session targeted on the gallbladder and another group had two BESWL sessions targeted on the gallbladder. The third group had one BESWL session targeted on implanted gallbladder stones and the fourth group had one BESWL session targeted on the region of the common bile duct (CBD). Half of each group were sacrificed on the day of lithotripsy and half 1 week later. Post-mortem examinations were performed. Each implanted gallstone had fragmented. There were no findings attributable to BESWL in 11 animals. Three animals had pulmonary haemorrhagic spots (the largest was 10 mm in diameter) and one had a submucosal CBD petechia; these findings were attributable to BESWL. In two animals, microscopic haemorrhage associated with bronchopneumonia (usually present in our pig population) was more prominent than usual. This was possibly attributable to BESWL. The swine's deep posterior costophrenic sulcus makes it difficult to avoid the lung base during BESWL in swine. We conclude that this BESWL device can fragment gallstones without causing clinically significant soft-tissue damage.

Animals↗

PubMed2005

Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory.

Four main theories on the pathophysiology of generalized absence seizures have been proposed. The "centrencephalic" theory, proposed in 1954, suggested that discharges originate from a deep-seated diffusely projecting subcortical pacemaker in the midline thalamus. This concept was refined in 1991 with the "thalamic clock" theory, implying that the reticular thalamic nucleus contains the pacemaker cells for the thalamic clock, imposing its rhythm to the cortex. According to other investigators, however, the cortex seems to play a leading role. They suggested that spike-wave discharges have a focal onset in the cortex and are generalized through a rapid propagation. In the "corticoreticular" theory, postulated in 1968, spike-wave discharges are linked to the thalamocortical mechanisms that generate spindles. Rhythmic spindle oscillations generated in the thalamus are transformed into spike-wave discharges when the cortex is hyperexcitable. A 2002 study confirmed in epileptic rats that a functionally intact thalamocortical network is required for the generation of spike-wave discharges. The corticothalamic interrelationships were investigated by means of nonlinear association signal analyses of multiple spike-wave discharges. This showed a consistent focus within the perioral region of the somatosensory cortex. From this focus, seizure activity generalizes rapidly over the cortex. During the first cycles of the seizure the cortex drives the thalamus, while thereafter cortex and thalamus drive each other, thus amplifying and maintaining the rhythmic discharge. In this way the "cortical focus" theory for generalized absence epilepsy bridges cortical and thalamic theories.

Animals↗

PubMed2003

Inhibition of annexin V binding to cardiolipin and thrombin generation in an unselected population with venous thrombosis.

OBJECTIVE: To examine the effect on annexin V binding to cardiolipin (CL) and in vitro thrombin generation by plasma samples from an unselected population of patients with confirmed venous thrombosis and matched controls. The prevalence of autoimmune antiphospholipid antibodies (aPL) was also determined. METHODS: A total of 111 patients who presented to a single emergency room with symptoms suggestive of venous thromboembolic (VTE) disease were studied. In 34 patients the diagnosis of lower limb deep venous thrombosis (DVT) and/or pulmonary embolus (PE) was confirmed (VTE+ group). In the remaining 77 patients the diagnostic workup was negative (VTE- group). Plasma samples were collected prior to the initiation of anticoagulation and examined for IgG anticardiolipin (aCL), IgG anti-beta2-glycoprotein I (GPI), and IgG anti-prothrombin (aPT antibodies) by ELISA. In addition, the effect of individual patient and control plasma samples on annexin V binding to CL and on in vitro thrombin generation was determined by a competitive ELISA and a chromogenic assay, respectively. RESULTS: The prevalence and levels of IgG aCL, anti-beta2-GPI, and aPT antibodies were similar in the VTE+ and VTE- groups. However, plasma samples from the VTE+ group caused a significant inhibition of in vitro thrombin generation (mean +/- SD Z score: -0.66 +/- 0.97 vs 0.26 +/- 1.46; p < 0.001) and a concurrent but less impressive inhibition of annexin V binding to CL (mean +/- SD Z score: -2.53 +/- 1.44 vs -2.05 +/- 1.61; p = 0.123). Upon analyzing a panel of clinical and laboratory variables, only age and inhibition of thrombin generation were significantly associated with VTE disease. CONCLUSION: Our findings suggest that subtle abnormalities in annexin V physiology may contribute to the procoagulant state in patients with idiopathic venous thrombosis.

Annexin A5↗

PubMed2006

Ion permeation through the Na+,K+-ATPase.

P-type ATPase pumps generate concentration gradients of cations across membranes in nearly all cells. They provide a polar transmembrane pathway, to which access is strictly controlled by coupled gates that are constrained to open alternately, thereby enabling thermodynamically uphill ion transport (for example, see ref. 1). Here we examine the ion pathway through the Na+,K+-ATPase, a representative P-type pump, after uncoupling its extra- and intracellular gates with the marine toxin palytoxin. We use small hydrophilic thiol-specific reagents as extracellular probes and we monitor their reactions, and the consequences, with cysteine residues introduced along the anticipated cation pathway through the pump. The distinct effects of differently charged reagents indicate that a wide outer vestibule penetrates deep into the Na+,K+-ATPase, where the pathway narrows and leads to a charge-selectivity filter. Acidic residues in this region, which are conserved to coordinate pumped ions, allow the approach of cations but exclude anions. Reversing the charge at just one of those positions converts the pathway from cation selective to anion selective. Close structural homology among the catalytic subunits of Ca2+-, Na+,K+- and H+,K+-ATPases argues that their extracytosolic cation exchange pathways all share these physical characteristics.

Acrylamides↗

PubMed1993

Effect of pH on solubility and ionic state of lipopolysaccharide obtained from the deep rough mutant of Escherichia coli.

The dissociation of the highly aggregated form of lipopolysaccharide (LPS) from Gram-negative bacteria to the monomeric (or soluble) form is though to be the initial step in the activation of responding cells (macrophages, B-cells, neutrophils, monocytes, and endothelial cells) by LPS. This process is presently not adequately understood. Using the equilibrium dialysis apparatus and a highly purified and well-characterized radiolabeled deep rough chemotype LPS ([14C]ReLPS) from Escherichia coli D31m4, we have examined the effect of pH on its solubility (CT) and ionic states in aqueous media. The solubility range of [14C]ReLPS suspended in 50 mM Tris-HCl-100 mM KCl buffer (or 50 mM MES-100 mM KCl buffer at pH 6.5) was determined to be from (2.91 +/- 0.01) x 10(-8) to (4.55 +/- 0.07) x 10(-8) M over a pH range of 6.50-8.20, respectively. These experimental data satisfactorily fitted the curve generated by the solubility equation CT = S0(1 + K5/[H+])/([H+]/K4' + 1), where S0 is the concentration of the tetraanionic ReLPS, K5 is the dissociation constant of the tetraanionic ReLPS in solution, and K4' is the dissociation constant of the trianionic ReLPS at the surface of the solid particles in suspension. The increase in solubility of ReLPS with increase in pH from 7.00 to 8.20 is primarily caused by the formation of the pentaanionic form from the tetraanions. The pK5 (primarily the second dissociation of the 1-phosphate) of ReLPS was determined to be 8.58 from experimental data.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗

PubMed2003

Effects of temperature and turbulence on the predator-prey interactions between a heterotrophic flagellate and a marine bacterium.

Biotic and abiotic factors can influence interactions between microbial grazers and their prey, thus impacting both the cycling of biogenic carbon within the surface layer of the ocean and the export of carbon to the deep ocean and higher trophic levels. In this study, microcosm experiments were used to evaluate the combined effect of temperature and turbulence on the growth rate of a marine bacterium (Vibrio splendidus), a protistan predator (Paraphysomonas sp.), and the community grazing impact of Paraphysomonas sp. on V. splendidus. It was found that the artificial turbulence generated (1.35 x 10-1 cm2 s-3) significantly increased the rates of growth of Paraphysomonas sp. at high (>10 degrees C), but not low (<5 degrees C) temperatures, and that turbulence had no effect on the growth of V. splendidus. Both flagellate and bacterial growth were temperature dependent and decreased 4- to 6-fold as temperatures decreased from 15 to 0 degrees C. Bacterial grazing mortality by Paraphysomonas sp. was 1.3- to 2.5-fold greater in the turbulent than static treatments among all four temperatures, and the rates of cell-specific ingestion of bacteria by Paraphysomonas sp. was 2-fold greater at 15 and 10 degrees C in the turbulent than in the static treatment. Hence, this study shows that turbulence can influence nanoflagellate grazing at temperatures >5 degrees C and suggests that at low temperatures, increased viscosity may limit the size of organisms that can be affected by small-scale turbulence.

Animals↗

PubMed2005

A high current density DC magnetohydrodynamic (MHD) micropump.

This paper describes the working principle of a DC magnetohydrodynamic (MHD) micropump that can be operated at high DC current densities (J) in 75-microm-deep microfluidic channels without introducing gas bubbles into the pumping channel. The main design feature for current generation is a micromachined frit-like structure that connects the pumping channel to side reservoirs, where platinum electrodes are located. Current densities up to 4000 A m(-2) could be obtained without noticeable Joule heating in the system. The pump performance was studied as a function of current density and magnetic field intensity, as well as buffer ionic strength and pH. Bead velocities of up to 1 mm s(-1) (0.5 microL min(-1)) were observed in buffered solutions using a 0.4 T NdFeB permanent magnet, at an applied current density of 4000 A m(-2). This pump is intended for transport of electrolyte solutions having a relatively high ionic strength (0.5-1 M) in a DC magnetic field environment. The application of this pump for the study of biological samples in a miniaturized total analysis system (microTAS) with integrated NMR detection is foreseen. In the 7 T NMR environment, a minimum 16-fold increase in volumetric flow rate for a given applied current density is expected.

Electrochemistry↗

PubMed2026

AI echo INSIGHT study: A prospective blinded randomized trial of artificial intelligence echocardiogram interpretation.

BACKGROUND: Transthoracic echocardiography (TTE) is the most commonly performed cardiac imaging modality with over 30 million studies annually. Demand for timely expert interpretation continues to outpace capacity, creating diagnostic delays and inter-observer variability that impact patient care. Recent research has suggested computer vision artificial intelligence (AI) models can generate accurate preliminary comprehensive TTE reports, however, prospective evaluation is needed to determine whether AI-assisted TTE interpretation can improve clinician efficiency while preserving diagnostic accuracy. METHODS: AI ECHO INSIGHT is a prospective randomized blinded clinical trial conducted at Kaiser Permanente Northern California that will evaluate 1200 historical TTE studies (1000 consecutive unselected studies plus 200 with moderate or greater valvular disease) interpreted using three workflows: (1) AI-generated preliminary report finalized by a blinded cardiologist (AI-assisted); (2) cardiologist-generated preliminary report finalized by a blinded cardiologist (cardiologist-assisted); and (3) sonographer-generated preliminary report finalized by a blinded cardiologist (sonographer-assisted). The primary outcome is the rate of substantial change between preliminary and final reports, comparing the AI-assisted workflow to the pooled cardiologist-assisted and sonographer-assisted workflows. Secondary outcomes include cardiologist interpretation time for report finalization, superiority testing for diagnostic accuracy, and reporting consistency. CONCLUSION: AI ECHO INSIGHT is a prospective randomized blinded clinical trial evaluating the clinical impact of AI-assisted TTE interpretation on diagnostic accuracy, cardiologist efficiency, and reporting consistency in real-world echocardiography workflows. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT07229300.

Humans↗

PubMed1998

Generation of ligand binding sites in T4 lysozyme by deficiency-creating substitutions.

Several variants of T4 lysozyme have been identified that sequester small organic ligands in cavities or clefts. To evaluate potential binding sites for non-polar molecules, we screened a number of hydrophobic large-to-small mutants for stabilization in the presence of benzene. In addition to Leu99-->Ala, binding was indicated for at least five other mutants. Variants Met102-->Ala and Leu133-->Gly, and a crevice mutant, Phe104-->Ala, were further characterized using X-ray crystallography and thermal denaturation. As predicted from the shape of the cavity in the benzene complex, mutant Leu133-->Gly also bound p-xylene. We attempted to enlarge the cavity of the Met102-->Ala mutant into a deep crevice through an additional substitution, but the double mutant failed to bind ligands because an adjacent helix rearranged into a non-helical structure, apparently due to the loss of packing interactions. In general, the protein structure contracted slightly to reduce the volume of the void created by truncating substitutions and expanded upon binding the non-polar ligand, with shifts similar to those resulting from the mutations.A polar molecule binding site was also created by truncating Arg95 to alanine. This creates a highly complementary buried polar environment that can be utilized as a specific "receptor" for a guanidinium ion. Our results suggest that creating a deficiency through truncating mutations of buried residues generates "binding potential" for ligands with characteristics similar to the deleted side-chain. Analysis of complex and apo crystal structures of binding and non-binding mutants suggests that ligand size and shape as well as protein flexibility and complementarity are all determinants of binding. Binding at non-polar sites is governed by hydrophobicity and steric interactions and is relatively permissive. Binding at a polar site is more restrictive and requires extensive complementarity between the ligand and the site.

Bacteriophage T4↗

PubMed2005

Annual lipid cycles in hibernators: integration of physiology and behavior.

Mammalian hibernation is a temporary suspension of euthermia allowing endotherms to undergo reversible hypothermia and generate a marked savings in energy expenditure. In most fat-storing hibernator species, seasonal changes in food intake, triacylglycerol deposition, metabolism, and reproductive development are controlled by a circannual clock. In ground-dwelling sciurid rodents (ground squirrels and marmots), for example, energy intake increases during a summer body mass gain phase, and toward the end of this phase metabolic rate also begins to decrease, resulting in a profound increase in lipid deposition as fat. Increased activity of lipogenic hormones and enzymes correspond with this increase. The hibernation mass loss phase begins after the body mass peak in the fall and ends in spring. During this phase, stored lipids are slowly utilized in a programmed manner by undergoing deep torpor or hibernation during which the hypothalamic setpoint for body temperature is typically reduced to just above 0 degrees C. Throughout the hibernation season, bouts of deep torpor are punctuated by periodic arousals in which brown adipose tissue thermogenesis plays a critical role. Lipid oxidation nearly exclusively fuels deep torpor and most of the rewarming process. The fatty acid composition of stored lipids can affect the depth and duration of deep torpor, and saturated fatty acids may be preferentially used during hibernation, whereas polyunsaturated fatty acids may be preferentially retained. Female and underweight male hibernators terminate hibernation in spring when aboveground food becomes available; in contrast, heavier males with sufficient lipid reserves spontaneously terminate hibernation several weeks before females and independent of food availability. Mating occurs shortly after emergence from hibernation, and the lipid cycle begins again with the completion of reproduction. Lipid deposition and mobilization, temperature regulation, reproduction, and circannual timing are intimately interdependent. The unique manner in which they are controlled during the annual cycle, especially lipid reserves, makes hibernators valuable and promising models for research into the mechanisms underlying these processes in all mammals.

Adipose Tissue↗

PubMedDate not supplied

The great gate: control of sensory information flow to the cerebellum.

An evident feature of the physiology of the inferior olivary nucleus is modulation of the responsiveness of neurons to peripheral stimulation by the behavioral state of the subject animal. The olivary response to self-generated sensory inputs, as well as to input predictable from association with other stimuli, is suppressed. This suppression occurs in part at the level of the inferior olivary nucleus itself. On the other hand, the cells respond readily to sensory inputs that are not anticipated. On a cellular level inferior olivary neurons exhibit two properties that might account for information gating. The first one is the organization of synaptic inputs on olivary spines in glomerular structures, where extrinsic inhibitory and excitatory inputs, confined to the same olivary dendritic spine, can efficiently cancel each other if they arrive within a certain time window. About half of the inhibitory inputs to olivary glomeruli originate in the deep cerebellar nuclei and are regarded as an inhibitory feedback. The second property is subthreshold membrane potential oscillations, a property of the electrotonically coupled olivary network. Extrinsic synaptic inputs to the nucleus modulate the subthreshold oscillations, and consequently, the response properties of olivary neurons. A considerable amount of indirect evidence indicates that the occurrence of oscillations corresponds to states of increased responsiveness of the neurons to peripheral stimulation. The sensory filtering role of the inferior olivary nucleus invites comparison between the cerebellum and cerebellar-like structures. This comparison sheds important light on the function of the cerebellum.

Afferent Pathways↗