A 10-fr Ultrasound Catheter With Integrated Micromotor For 4-d Intracardiac Echocardiography
ablation; Acoustics; array; atrial-fibrillation; catheterization; Echocardiography; electrophysiology; Engineering; guidance; in-vivo; pulmonary vein isolation; real-time; transseptal
We developed prototype real-time 3-D intracardiac echocardiography catheters with integrated micromotors, allowing internal oscillation of a low-profile 64-element, 6.2-MHz phased-array transducer in the elevation direction. Components were designed to facilitate rotation of the array, including a low-torque flexible transducer interconnect and miniature fixtures for the transducer and micromotor. The catheter tip prototypes were integrated with two-way deflectable 10-Fr catheters and used in in vivo animal testing at multiple facilities. The 4-D ICE catheters were capable of imaging a 90 degrees azimuth by up to 180 degrees elevation field of view. Volume rates ranged from 1 vol/sec (180 degrees elevation) to approximately 10 vol/sec (60 degrees elevation). We successfully imaged electrophysiology catheters, atrial septal puncture procedures, and detailed cardiac anatomy. The elevation oscillation enabled 3-D visualization of devices and anatomy, providing new clinical information and perspective not possible with current 2-D imaging catheters.
Lee W; Griffin W; Wildes D; Buckley D; Topka T; Chodakauskas T; Langer M; Calisti S; Bergstol S; Malacrida J P; Lanteri F; Maffre J; McDaniel B; Shivkumar K; Cummings J; Callans D; Silvestry F; Packer D
Ieee Transactions on Ultrasonics Ferroelectrics and Frequency Control
2011
2011-07
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1109/tuffc.2011.1967" target="_blank" rel="noreferrer noopener">10.1109/tuffc.2011.1967</a>
Hyperpolarizing And Depolarizing Gaba-a Receptor-mediated Dendritic Inhibition In Area Ca1 Of The Rat Hippocampus
activity-dependent disinhibition; cortical-neurons; depression; electrophysiology; gamma-aminobutyric acid; lacunosum-moleculare interneurons; morphology; Neurosciences & Neurology; Physiology; pyramidal cells-invitro; responses; voltage-clamp
1. Gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABA(A) and late, GABA(B) receptor or-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABA(A) receptor antagonist bicuculline methiodide (BMI; 30-mu-M) and were not changed by the GABA(B) receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35 348; 0.1-1.0 mM). CGP 35 348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABA(A) receptor-mediated population IPSPs (GABA(A), fast pIPSPs) and that late field potentials are GABA(B) receptor-mediated population IPSPs (GABA(B), late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration ([Cl-1]o) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35 348 (0.40. 8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABA(A) current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4-aminopyridine (50-100-mu-M), DNQX and APV long-lasting depolarizing GABA(A) receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs. 7. These results suggest that activation of GABA(A) receptors located on pyramidal neuron apical and basal dendrites produces outward Cl-1 current and hyperpolarizing IPSPs. This suggests that depolarizing responses to dendritic GABA application and orthodromic activation in area CA1 do not result from inward chloride current.
Lambert N A; Borroni A M; Grover L M; Teyler T J
Journal of Neurophysiology
1991
1991-11
Journal Article or Conference Abstract Publication
n/a
Laminar Pattern Of Synaptic Activity In Rat Primary Visual-cortex - Comparison Of In-vivo And In-vitro Studies Employing The Current Source Density Analysis
anuran cerebellum; area ca1; cerebral-cortex; connections; current source density; electrically evoked-potentials; electrophysiology; field; multiple unit-activity; neocortex; neurons; Neurosciences & Neurology; organization; potentials; rat; slice; striate cortex
In the present study we employed current source density analysis to study the major excitatory/inhibitory pathways in rat primary visual cortex in vivo and in vitro. A natural photic stimulus was used in vivo and served as a baseline for understanding the results obtained from in vivo and in vitro studies employing electrical stimulation of the white matter. The temporal pattern of synaptic activity in the cortex revealed an early excitation, characterized by sinks of short duration and high amplitude, that was followed by inhibition, characterized by long lasting, low amplitude active sources. The spatial pattern of this synaptic activity displayed early excitatory inputs to layer IV and lower layer III. Supragranular layers exhibited synaptic activity of longer latency at more superficial layers. The excitatory activity of the infragranular layers was delayed relative to that in layer IV. This spatial and temporal pattern of synaptic activity supports the model of sequential information processing in visual cortex. Based on the results of electrical and photic stimulations in vivo we conclude that electrical stimulation of white matter activate the thalamo-cortical input which results in a similar laminar pattern of postsynaptic activity evoked by photic stimulation. Electrical stimulation revealed additional antidromic and anti-orthodromic activity (collaterals of descending axons to white matter), resulting in the early fast components and the additional activity in layer VI. The major differences between in vivo and in vitro laminar pattern of synaptic activity (applying electrical stimulation) were reduced synaptic activity in layer IV and increased synaptic activity in the infragranular layers in the in vitro preparation. We concluded that the visual cortex slice preparation preserves the major pathways and electrophysiological function of this area. The technical advantages of the cortical slice preparation will facilitate studies and provide additional insight into this complex cortical network.
Kenanvaknin G; Teyler T J
Brain Research
1994
1994-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0006-8993(94)91421-4" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(94)91421-4</a>
Identification And Ablation Of Dormant Conduction In Atrial Fibrillation Using Adenosine
Ablation; Adenosine; antiarrhythmic-drug therapy; Arrhythmias; Atrial fibrillation; catheter ablation; Electrophysiology; end-points; expert consensus; follow-up; General & Internal Medicine; patient-management; procedural techniques; pulmonary vein isolation; recommendations; statement; surgical ablation
Luni F K; Khan A R; Singh H; Riaz H; Malik S A; Khawaja O; Farid T; Cummings J; Taleb M
American Journal of the Medical Sciences
2018
2018-01
Journal Article or Conference Abstract Publication
n/a
Metabotropic glutamate receptor antagonist, (R,S)-alpha-methyl-4-carboxyphenyglycine, blocks two distinct forms of long-term potentiation in area CA1 of rat hippocampus.
Animals; Rats; Electric Stimulation; In Vitro Techniques; Electrophysiology; Excitatory Amino Acid Antagonists/*pharmacology; Long-Term Potentiation/*drug effects; Hippocampus/drug effects/*physiology; Benzoates/*pharmacology; Calcium Channels/drug effects/metabolism/physiology; Glycine/*analogs & derivatives/pharmacology; Ion Channel Gating/drug effects; Receptors; Metabotropic Glutamate/*antagonists & inhibitors
The necessity of metabotropic glutamate receptors (mGluRs) in the induction of long-term potentiation (LTP) has recently been questioned. We examined the effect of (R,S)-alpha-methyl-4-caboxyphenylglycine (MCPG), a selective mGluR antagonist, on two independent forms of LTP. One form induced by a 25 Hz/1 s tetanus is solely N-methyl-D-aspartate (NMDA) receptor-dependent. The other form induced by four 200 Hz/0.5 s bursts in the presence of APV is NMDA receptor-independent. In both paradigms the presence of MCPG prevented the induction of LTP by afferent activation.
Little Z; Grover L M; Teyler T J
Neuroscience letters
1995
1995-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Aspartame exposure and in vitro hippocampal slice excitability and plasticity.
Female; Time Factors; Animals; Rats; Electric Stimulation; Electrophysiology; Neurons/drug effects; Aspartame/*toxicity; Dipeptides/*toxicity; Hippocampus/*drug effects/physiopathology; Neuronal Plasticity/*drug effects
Aspartame (APM) is a low-calorie sweetener recently approved and released for widespread use in the United States. However, concerns still exist that APM consumption may be responsible for adverse neurological and psychological effects in some people. In addition, recent reports indicate that APM exposure may alter regional brain neurotransmitter levels. The present study assessed the effects of APM and its amino acid moieties on rat hippocampal slice excitability and plasticity. Specifically, tests of excitatory systems, inhibitory systems, and synaptic plasticity (induction of long-term potentiation–LTP) were administered postexposure. Exposures of 0.01, 0.1, 1, and 10 mM APM potentiated the response of hippocampal CA1 pyramidal cells, but had no apparent effect on local inhibitory systems. APM exposure did not block the establishment of LTP at any dose despite the potentiation of pyramidal cell response observed postexposure. In addition, 0.1 mM phenylalanine (PHE) produced a greater increase in excitability than that produced by an equivalent dose of APM, 0.1 mM aspartic acid (ASP) and 0.1 mM phenylalanine methyl ester (PM) produced effects comparable to those produced a smaller, but reliable, change in hippocampal CA1 excitability relative to baseline. Like APM, none of the amino acids produced detectable changes in inhibitory systems or neuronal plasticity.
Fountain S B; Hennes S K; Teyler T J
Fundamental and applied toxicology : official journal of the Society of Toxicology
1988
1988-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/toxsci/11.1.221" target="_blank" rel="noreferrer noopener">10.1093/toxsci/11.1.221</a>
A slice preparation preserving the callosal projection to contralateral visual cortex.
Female; Male; Animals; Rats; *Synaptic Transmission; In Vitro Techniques; Electrophysiology; Corpus Callosum/*physiology; Neurology/instrumentation; Visual Cortex/*physiology; Inbred Strains
Due to the curved path they follow, the visual callosal projections to areas OC1 and OC2 of the rat visual cortex have been inaccessible to studies using brain slices. In this paper we describe a new slice preparation in which a curved cutting blade was used to obtain slices in which callosal fibers projecting to OC1 or OC2 are preserved. Stimulation of the contralateral white matter resulted in EPSPs recorded in layer II/III and V cells of OC2 studied with intracellular recording. Current source density analysis of extracellular field potentials collected in OC1 and OC2 revealed laminar current sink patterns paralleling the laminar distribution of callosal terminations reported by Miller and Vogt (Dev. Brain Res., 14 (1984) 304-309). Exposure of slices to 2 mM kynurenic acid reversibly abolished current sinks in OC1 recorded in response to callosal stimulation indicating that glutamate receptors mediate the response of OC1 to callosal afferent activity. This new slicing technique can be readily adapted to study other systems in the nervous system in which neural processes follow curved trajectories.
Berry R L; Nowicky A; Teyler T J
Journal of neuroscience methods
1990
1990-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0165-0270(90)90021-7" target="_blank" rel="noreferrer noopener">10.1016/0165-0270(90)90021-7</a>
Developmental hearing loss impairs signal detection in noise: putative central mechanisms.
masking; auditory cortex; conductive hearing loss; electrophysiology; gerbil; intracellular; noise; signal detection
Listeners with hearing loss have difficulty processing sounds in noisy environments. This is most noticeable for speech perception, but is reflected in a basic auditory processing task: detecting a tonal signal in a noise background, i.e., simultaneous masking. It is unresolved whether the mechanisms underlying simultaneous masking arise from the auditory periphery or from the central auditory system. Poor detection in listeners with sensorineural hearing loss (SNHL) is attributed to cochlear hair cell damage. However, hearing loss alters neural processing in the central auditory system. Additionally, both psychophysical and neurophysiological data from normally hearing and impaired listeners suggest that there are additional contributions to simultaneous masking that arise centrally. With SNHL, it is difficult to separate peripheral from central contributions to signal detection deficits. We have thus excluded peripheral contributions by using an animal model of early conductive hearing loss (CHL) that provides auditory deprivation but does not induce cochlear damage. When tested as adults, animals raised with CHL had increased thresholds for detecting tones in simultaneous noise. Furthermore, intracellular in vivo recordings in control animals revealed a cortical correlate of simultaneous masking: local cortical processing reduced tone-evoked responses in the presence of noise. This raises the possibility that altered cortical responses which occur with early CHL can influence even simple signal detection in noise.
Gay Jennifer D; Voytenko Sergiy V; Galazyuk Alexander V; Rosen Merri J
Frontiers in systems neuroscience
2014
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3389/fnsys.2014.00162" target="_blank" rel="noreferrer noopener">10.3389/fnsys.2014.00162</a>
Roles of inhibition in complex auditory responses in the inferior colliculus: inhibited combination-sensitive neurons.
Acoustic Stimulation; Action Potentials/drug effects/physiology; Afferent/drug effects/*physiology; Animals; Auditory; Auditory Pathways/drug effects/*physiology; Bicuculline/pharmacology; Brain Stem/drug effects/*physiology; Chiroptera; Electrophysiology; Evoked Potentials; GABA-A Receptor Antagonists; GABA-A/physiology; Glycine/antagonists & inhibitors/physiology; Inferior Colliculi/*physiology; Neural Inhibition/drug effects/*physiology; Neurons; Receptors; Strychnine/pharmacology
We studied the functional properties and underlying neural mechanisms associated with inhibitory combination-sensitive neurons in the mustached bat's inferior colliculus (IC). In these neurons, the excitatory response to best frequency tones was suppressed by lower frequency signals (usually in the range of 12-30 kHz) in a time-dependant manner. Of 143 inhibitory units, the majority (71%) were type I, in which low-frequency sounds evoked inhibition only. In the remainder, however, the low-frequency inhibitory signal also evoked excitation. Of these, excitation preceded the inhibition in type E/I units (16%), whereas in type I/E units (13%), excitation followed the inhibition. Type E/I and I/E units were distinct in the tuning and threshold sensitivity of low-frequency responses, whereas type I units overlapped the other types in these features. In 71 neurons, antagonists to receptors for glycine [strychnine (STRY)] or GABA [bicuculline (BIC)] were applied microiontophoretically. These antagonists failed to eliminate combination-sensitive inhibition in 92% (STRY), 93% (BIC), and 87% (BIC + STRY) of the type I units tested. However, inhibition was reduced in many neurons. Results were similar for type E/I and I/E inhibitory neurons. The results indicate that there are distinct populations of combination-sensitive inhibited neurons in the IC and that these populations are at least partly independent of glycine or GABAA receptors in the IC. We propose that these populations originate in different brain stem auditory nuclei, that they may be modified by interactions within the IC, and that they may perform different spectrotemporal analyses of vocal signals.
Nataraj Kiran; Wenstrup Jeffrey J
Journal of neurophysiology
2006
2006-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.01148.2005" target="_blank" rel="noreferrer noopener">10.1152/jn.01148.2005</a>
Intracellular recording reveals temporal integration in inferior colliculus neurons of awake bats.
Acoustic Stimulation; Animals; Chiroptera/*physiology; Data Interpretation; Electrophysiology; Excitatory Postsynaptic Potentials/physiology; Inferior Colliculi/cytology/*physiology; Inhibitory Postsynaptic Potentials/physiology; Microelectrodes; Neurons/*physiology; Pitch Perception; Statistical
The central nucleus of the inferior colliculus (IC) is a major integrative center in the central auditory system. It receives information from both the ascending and descending auditory pathways. To determine how single IC neurons integrate information over a wide range of sound frequencies and sound levels, we examined their intracellular responses to frequency-modulated (FM) sounds in awake little brown bats (Myotis lucifugus). Postsynaptic potentials were recorded in response to downward FM sweeps of the range typical for little brown bats (80-20 kHz) and to three FM subcomponents (80-60, 60-40, and 40-20 kHz). The majority of recorded neurons responded to the 80- to 20-kHz downward FM sweep with a complex response. In this response an initial hyperpolarization was followed by depolarization with or without spike followed by hyperpolarization. Intracellular recordings in response to three FM subcomponents revealed that these neurons receive excitatory and inhibitory inputs from a wide range of sound frequencies. One third of IC neurons performed nearly linear temporal summation across a wide range of sound frequencies, whereas two thirds of IC neurons exhibited nonlinear summation with different degrees of nonlinearity. Some IC neurons showed different latencies of postsynaptic potentials in response to different FM subcomponents. Often responses to the later FM subcomponent occurred before responses to the earlier ones. This phenomenon may be responsible for response selectivity of IC neurons to FM sweeps.
Voytenko S V; Galazyuk A V
Journal of neurophysiology
2007
2007-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.00976.2006" target="_blank" rel="noreferrer noopener">10.1152/jn.00976.2006</a>
Specificity of metabotropic glutamate receptor 2 coupling to G proteins.
Amino Acid; Amino Acid Sequence; Animals; Calcium/metabolism; Electrophysiology; Gi-Go/metabolism; GTP-Binding Protein alpha Subunits; GTP-Binding Proteins/*metabolism; Metabotropic Glutamate/*metabolism; Molecular Sequence Data; Neurons/*drug effects/metabolism; Pertussis Toxin/*pharmacology; Rats; Receptors; Sequence Homology; Superior Cervical Ganglion/cytology; Wistar
Metabotropic glutamate receptor 2 (mGluR2) is a class 3 G protein-coupled receptor and an important mediator of synaptic activity in the central nervous system. Previous work demonstrated that mGluR2 couples to pertussis toxin (PTX)-sensitive G proteins. However, the specificity of mGluR2 coupling to individual members of the G(i/o) family is not known. Using heterologously expressed mGluR2 in rat sympathetic neurons from the superior cervical ganglion (SCG), the mGluR2/G protein coupling profile was characterized by reconstituting coupling in PTX-treated cells expressing PTX-insensitive mutant Galpha proteins and Gbetagamma. By employing this method, it was demonstrated that mGluR2 coupled strongly with Galphaob, Galphai1, Galphai2, and Galphai3, although coupling to Galphaoa was less efficient. In addition, mGluR2 did not seem to couple to the most divergent member of the G(i/o) family, Galphaz, although Galphaz coupled strongly to the endogenous alpha2 adrenergic receptor. To determine which Galpha proteins may be natively expressed in SCG neurons, the presence of mRNA for various Galpha proteins was tested using reverse transcription-polymerase chain reaction. Strong bands were detected for all members of the G(i/o) family (Galphao, Galphai1, Galphai2, Galphai3, Galphaz) as well as for Galpha11 and Galphas. A weak signal was detected for Galphaq and no Galpha15 mRNA was detected.
Kammermeier Paul J; Davis Margaret I; Ikeda Stephen R
Molecular pharmacology
2003
2003-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1124/mol.63.1.183" target="_blank" rel="noreferrer noopener">10.1124/mol.63.1.183</a>
The effects of anticonvulsant drugs on NMDA-EPSP, AMPA-EPSP, and GABA-IPSP in the rat hippocampus.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/*pharmacology; Animals; Anticonvulsants/*pharmacology; Electrophysiology; gamma-Aminobutyric Acid/*pharmacology; Hippocampus/*drug effects/physiology; Inbred Strains; Male; N-Methylaspartate/*pharmacology; Phenobarbital/pharmacology; Phenytoin/pharmacology; Rats; Valproic Acid/pharmacology
The effects of phenobarbital, phenytoin, and valproic acid on pharmacologically isolated NMDA-EPSP, AMPA-EPSP, and GABA-IPSPs were examined in rat hippocampal slices. Phenobarbital (0.05 mg/ml) had no effect on the NMDA-EPSP, but decreased the slope of the AMPA-EPSP by 13.4% and facilitated the GABA-IPSP slope by 77.12%. Phenytoin (0.02 mg/ml) had no effects on the NMDA-EPSP, AMPA-EPSP, or
Ko G Y; Brown-Croyts L M; Teyler T J
Brain research bulletin
1997
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0361-9230(96)00268-7" target="_blank" rel="noreferrer noopener">10.1016/s0361-9230(96)00268-7</a>
Tachykinin peptide-induced activation and desensitization of neurokinin 1 receptors.
Amino Acid Sequence; Animals; CHO Cells; Cricetinae; Down-Regulation/*drug effects; Electrophysiology; Ligands; Neurokinin-1/*agonists/*metabolism; Potassium/metabolism; Protein Binding; Rana catesbeiana; Receptors; Tachykinins/chemistry/*pharmacology
The actions of four tachykinins on inhibition and desensitization of the
Perrine S A; Bennett V J; Simmons M A
Peptides
2003
2003-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0196-9781(03)00064-0" target="_blank" rel="noreferrer noopener">10.1016/s0196-9781(03)00064-0</a>
Epileptic-like activity induces multiple forms of plasticity in hippocampal area CA1.
*Neuronal Plasticity; Animals; Calcium Channels; Electrophysiology; Epilepsy/chemically induced/*physiopathology; Hippocampus/*physiopathology; Ion Channels/physiology; L-Type/physiology; Long-Evans; Long-Term Potentiation/physiology; N-Methyl-D-Aspartate/metabolism; Potassium Chloride; Rats; Receptors; Synapses/physiology
Mesial temporal lobe epilepsy is a relatively common form of epilepsy that afflicts many thousands of people. It has been suggested that the development of primary and secondary foci may involve mechanisms similar to long-term potentiation (LTP). In vitro seizure models typically involve an increase in spontaneous asynchronous bursting activity (epileptiform activity) induced either by increasing excitation or decreasing inhibition. Previous experiments have indicated that these models often generate bursting activity that closely resembles epileptic activity. LTP is often observed following epileptiform activity. In area CA1 of the hippocampus two forms of LTP that are dependent on the activation of either the L-type voltage dependent calcium channel (vdccLTP) or the N-methyl-D-aspartate receptor/channel (nmdaLTP) have been described. It is unclear from previous experiments which type of LTP results from epileptiform activity. Recent evidence indicates that nmdaLTP is most likely a short-term type of plasticity while vdccLTP may be a long-lasting form of synaptic plasticity. Given the characteristics of vdccLTP it is a likely candidate mechanism to underlie the development and formation of secondary seizure foci. We have therefore tested the ability of epileptiform activity induced by elevated potassium chloride to induce multiple forms of LTP in area CA1 of the rat hippocampus. Elevation of extracellular potassium chloride resulted in spontaneous asynchronous bursting. The net result of the spontaneous asynchronous bursting was to induce a compoundLTP consisting of nmdaLTP and vdccLTP components.
Morgan S L; Teyler T J
Brain research
2001
2001-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0006-8993(01)02913-4" target="_blank" rel="noreferrer noopener">10.1016/s0006-8993(01)02913-4</a>
Canertinib induces ototoxicity in three preclinical models.
Animals; Antineoplastic Agents/*adverse effects/pharmacology; Antitumor; Auditory; Canertinib; Carcinoma; Drug Screening Assays; Ear; Electrophysiology; ERBB; ErbB Receptors/*antagonists & inhibitors; Female; Hair Cells; Hearing Loss/*chemically induced; Hearing/*drug effects; Inbred C57BL; Inbred CBA; Lung Neoplasms/drug therapy; Male; Mice; Morpholines/*adverse effects/pharmacology; Neuregulin-1/metabolism; Non-small cell lung cancer; Non-Small-Cell Lung/drug therapy; NRG1; Ototoxicity; Outer hair cell; Outer/*drug effects; Signal Transduction/drug effects; Zebrafish
Neuregulin-1 (NRG1) ligand and its epidermal growth factor receptor (EGFR)/ERBB family regulate normal cellular proliferation and differentiation in many tissues including the cochlea. Aberrant NRG1 and ERBB signaling cause significant hearing impairment in mice. Dysregulation of the same signaling pathway in humans is involved in certain types of cancers such as breast cancer or non-small cell lung cancer (NSCLC). A new irreversible pan-ERBB inhibitor, canertinib, has been tested in clinical trials for the treatment of refractory NSCLC. Its possible ototoxicity was unknown. In this study, a significant dose-dependent canertinib ototoxicity was observed in a zebrafish model. Canertinib ototoxicity was further confirmed in two mouse models with different genetic backgrounds. The data strongly suggested an evolutionally preserved ERBB molecular mechanism underlying canertinib ototoxicity. Thus, these results imply that clinical monitoring of hearing loss should be considered for clinical testing of canertinib or other pan-ERBB inhibitors.
Tang Jian; Qian Yi; Li Hui; Kopecky Benjamin J; Ding Dalian; Ou Henry C; DeCook Rhonda; Chen Xiaojie; Sun Zhenyu; Kobel Megan; Bao Jianxin
Hearing research
2015
2015-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.heares.2015.07.002" target="_blank" rel="noreferrer noopener">10.1016/j.heares.2015.07.002</a>
Prenatal cocaine exposure leads to enhanced long-term potentiation in region CA1 of hippocampus.
*Prenatal Exposure Delayed Effects; Animals; Cocaine/*administration & dosage/pharmacology; Electrophysiology; Female; Hippocampus/*drug effects/physiology; In Vitro Techniques; Long-Term Potentiation/*drug effects; Narcotics/*administration & dosage/pharmacology; Neuronal Plasticity/drug effects; Pregnancy; Rabbits; Reference Values; Synapses/drug effects
Cocaine use by pregnant women is currently of concern for its social and economic impact. Clinical studies of cocaine exposed offspring are limited by methodological constraints. In this study we used a rabbit model to examine the effects of gestational cocaine exposure on substrates of learning and memory. Rabbits, 30 to 40 days old, were examined for alterations in synaptic plasticity using an intact hippocampal slice preparation. Extracellular recordings revealed in utero cocaine exposure predisposed slices to larger long-term potentiation compared to controls.
Little J Z; Teyler T J
Brain research. Developmental brain research
1996
1996-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0165-3806(95)00187-5" target="_blank" rel="noreferrer noopener">10.1016/0165-3806(95)00187-5</a>
Responses to combinations of tones in the nuclei of the lateral lemniscus.
Acoustic Stimulation/methods; Animals; Auditory Pathways/*physiology; Brain Stem/*physiology; Chiroptera; Electrophysiology; Neurons/physiology; Reaction Time/physiology
Combination-sensitive neurons integrate specific spectral and temporal elements in biologically important sounds, and they may underlie the analysis of biosonar and social vocalizations. Combination-sensitive neurons are found in the forebrain of a variety of vertebrates. In the mustached bat, they also occur in the central nucleus of the inferior colliculus (ICC). However, it is not known where combination-sensitive response properties emerge. To address this question, we used a two-tone paradigm to examine responses of single units to combination stimuli in a brainstem structure, the nuclei of the lateral lemniscus (NLL). We recorded and histologically localized 101 single units in the NLL. The majority (82%) of units had a single excitatory frequency tuning curve. Seven units had two separate excitatory frequency tuning curves but displayed no combinatorial interaction. Twelve units were combination-sensitive. Of these, three units were facilitated by the combination of two separate frequency bands and nine units were inhibited by combinatorial stimuli. The three facilitatory neurons had excitatory responses tuned to the second harmonic constant frequency (CF2, 57-60 kHz) component of the biosonar signal and were facilitated by a second signal within the first harmonic (Hl, 24-30 kHz) of the biosonar call. Most of the inhibitory interactions occurred between signals in the frequency bands associated with the frequency-modulated (FM) components of the biosonar call. The strongest combinatorial effects (facilitatory and inhibitory) were elicited by simultaneous onset of the two signals (i.e., 0 ms delay). All combination-sensitive units were in the intermediate nucleus of the NLL (INLL), which in bats is a hypertrophied structure that projects strongly to combination-sensitive neurons in the ICC. Thus, the combination-sensitive neurons in the INLL may impart their response properties onto ICC neurons. However, the small number of facilitatory combination-sensitive neurons in the NLL suggests that the majority of these combinatorial responses originate in the ICC.
Portfors C V; Wenstrup J J
Journal of the Association for Research in Otolaryngology : JARO
2001
2001-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s101620010057" target="_blank" rel="noreferrer noopener">10.1007/s101620010057</a>
Depotentiation of vdccLTP requires NMDAR activation.
2-Amino-5-phosphonovalerate/pharmacology; Animals; Calcium Channel Blockers/*pharmacology; Calcium Channels/drug effects/*physiology; Electric Stimulation; Electrophysiology; Hippocampus/*physiology; Long-Evans; Long-Term Potentiation/*physiology; Male; N-Methyl-D-Aspartate/drug effects/*physiology; Nifedipine/*pharmacology; Organ Culture Techniques; Rats; Receptors; Synaptic Transmission/*physiology
Long-term potentiation is an enduring increase in synaptic efficacy following repeated stimulation of afferent fibers that is thought to underlie memory. In area CA1 of the hippocampus at least two forms of synaptic potentiation coexist at the same synapses; nmdaLTP and vdccLTP. NmdaLTP is induced by Ca2+ entry through NMDARs and is dependent on serine/threonine kinase activation, while vdccLTP is induced through Ca2+ entry through VDCCs and is dependent on tyrosine kinase activation. Depotentiation is a mechanism known to reverse nmdaLTP through phosphatase activation. The depotentiation of vdccLTP has not been previously investigated. We used hippocampal slices (area CA1) from male Long-Evans rats to induce vdccLTP with a 200-Hz tetanus in the presence of 50 microM APV. The 200-Hz tetanus resulted in a slowly developing vdccLTP that remained stable for at least 30 min. Thirty minutes after vdccLTP was induced, a low-frequency tetanus (3, 10, 20, 30, or 40 Hz) was applied in the presence of APV in an attempt to depotentiate vdccLTP. The 3- and 10-Hz low-frequency tetani resulted in no depotentiation. The 20- and 30-Hz tetani partially depotentiated vdccLTP (by approximately 13%), whereas the 40-Hz tetanus resulted in further potentiation. When APV was washed out prior to the 3-Hz low-frequency tetanus, the vdccLTP was completely depotentiated–presumably by NMDAR mechanisms. Our results indicate that vdccLTP is resistant to depotentiation under low-frequency stimulation conditions that readily depotentiate nmdaLTP. As tetanus frequencies are increased a small depotentiation is observed, suggesting that vdccLTP can be depotentiated to a small extent. When NMDARs are unblocked, vdccLTP can be completely depotentiated by a 3-Hz low-frequency tetanus, suggesting that vdccLTP can be depotentiated via activation of NMDAR mechanisms.
Morgan S L; Coussens C M; Teyler T J
Neurobiology of learning and memory
2001
2001-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/nlme.2001.4016" target="_blank" rel="noreferrer noopener">10.1006/nlme.2001.4016</a>
Presynaptic mechanism for heterosynaptic, posttetanic depression in area CA1 of rat hippocampus.
Afferent/drug effects; Animals; Electric Stimulation; Electrophysiology; Evoked Potentials/physiology; Glutamate/drug effects; Glutamates/pharmacology; Glutamic Acid; Hippocampus/drug effects/*physiology; In Vitro Techniques; Membrane Potentials/physiology; N-Methyl-D-Aspartate/antagonists & inhibitors; Neuronal Plasticity/drug effects/physiology; Neurons; Presynaptic/drug effects/*physiology; Pyramidal Cells/drug effects; Rats; Receptors; Synapses/drug effects/*physiology
Conditioning stimulation applied to afferent fibers in stratum radiatum or stratum oriens of hippocampal area CA1 produced heterosynaptic, posttetanic depression (PTD) of excitatory postsynaptic potentials (EPSPs). PTD amounted to a
Grover L M; Teyler T J
Synapse (New York, N.Y.)
1993
1993-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/syn.890150207" target="_blank" rel="noreferrer noopener">10.1002/syn.890150207</a>