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Anita F Quigley,
Joselito M Razal,
Magdalena Kita,
Rohoullah Jalili,
Amy Gelmi,
Anthony Penington,
Raquel Ovalle-Robles,
Ray H Baughman, Graeme M Clark,
Gordon G Wallace,
Robert M I Kapsa
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Anita F Quigley,
Joselito M Razal,
Magdalena Kita,
Rohoullah Jalili,
Amy Gelmi,
Anthony Penington,
Raquel Ovalle-Robles,
Ray H Baughman, Graeme M Clark,
Gordon G Wallace,
Robert M I Kapsa
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ABSTRACT: In this study, nanostructured conductive platforms synthesized from aligned multiwalled carbon nanotubes and polypyrrole are investigated as myo-regenerative scaffolds. Myotube formation follows a linear path on the platforms coinciding with extent of nanotopography. In addition, electrical stimulation enhances myo-nuclear number and differentiation. These studies demonstrate that conductive polymer platforms can be used to influence muscle cell behaviour through nanostructure and electrical stimulation.
Advanced healthcare materials. 11/2012; 1(6):801-8.
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David A X Nayagam,
Richard A Williams,
Jun Chen,
Kylie A Magee,
Jennifer Irwin,
Justin Tan,
Peter Innis,
Ronald T Leung,
Sue Finch,
Chris E Williams, Graeme M Clark,
Gordon G Wallace
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ABSTRACT: In vivo host responses to an electrode-like array of aligned carbon nanotubes (ACNTs) embedded within a biopolymer sheet are reported. This biocompatibility study assesses the suitability of immobilized carbon nanotubes for bionic devices. Inflammatory responses and foreign-body histiocytic reactions are not substantially elevated when compared to negative controls following 12 weeks implantation. A fibrous capsule isolates the implanted ACNTs from the surrounding muscle tissue. Filamentous nanotube fragments are engulfed by macrophages, and globular debris is incorporated into the fibrous capsule with no further reaction. Scattered leukocytes are observed, adherent to the ACNT surface. These data indicate that there is a minimal local foreign-body response to immobilized ACNTs, that detached fragments are phagocytosed into an inert material, and that ACNTs do not attract high levels of surface fouling. Collectively, these results suggest that immobilized nanotube structures should be considered for further investigation as bionic components.
Small 02/2011; 7(8):1035-42. · 8.35 Impact Factor
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ABSTRACT: This review describes the current concept of pneumococcal meningitis in cochlear implant recipients based on recent laboratory studies. It examines possible routes of Streptococcus pneumoniae infection to the meninges in cochlear implant recipients. It also provides insights into fundamental questions concerning the pathophysiology of pneumococcal meningitis in implant recipients.
Medline/PubMed database; English articles after 1960. Search terms: cochlear implants, meningitis, pneumococcus, streptococcus pneumonia.
Narrative review. All articles relating to post-implant meningitis without any restriction in study designs were assessed and information extracted.
The incidence of pneumococcal meningitis in cochlear implant recipients is greater than that of an age-matched cohort in the general population. Based on the current clinical literature, it is difficult to determine whether cochlear implantation per se increases the risk of meningitis in subjects with no existing risk factors for acquiring the disease. As this question cannot be answered in humans, the study of implant-related infection must involve the use of laboratory animals in order for the research findings to be applicable to a clinical situation. The laboratory research demonstrated the routes of infection and the effects of the cochlear implant in lowering the threshold for pneumococcal meningitis.
The laboratory data complement the existing clinical data on the risk of pneumococcal meningitis post-cochlear implantation.
Otolaryngology Head and Neck Surgery 11/2010; 143(5 Suppl 3):S15-23. · 1.72 Impact Factor
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ABSTRACT: Both clinical data and laboratory studies demonstrated the risk of pneumococcal meningitis post-cochlear implantation. This review examines strategies to prevent post-implant meningitis.
Medline/PubMed database; English articles after 1980. Search terms: cochlear implants, pneumococcus meningitis, streptococcus pneumonia, immunization, prevention.
Narrative review. All articles relating to post-implant meningitis without any restriction in study designs were assessed and information extracted.
The presence of inner ear trauma as a result of surgical technique or cochlear implant electrode array design was associated with a higher risk of post-implant meningitis. Laboratory data demonstrated the effectiveness of pneumococcal vaccination in preventing meningitis induced via the hematogenous route of infection. Fibrous sealing around the electrode array at the cochleostomy site, and the use of antibiotic-coated electrode array reduced the risk of meningitis induced via an otogenic route.
The recent scientific data support the U.S. Food and Drug Administration recommendation of pneumococcal vaccination for the prevention of meningitis in implant recipients. Nontraumatic cochlear implant design, surgical technique, and an adequate fibrous seal around the cochleostomy site further reduce the risk of meningitis.
Otolaryngology Head and Neck Surgery 11/2010; 143(5 Suppl 3):S9-14. · 1.72 Impact Factor
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ABSTRACT: In this study the synergistic effect of delivering two neurotrophins simultaneously to encourage neuron survival and neurite elongation was explored. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) were incorporated into polypyrrole (PPy) during electrosynthesis and the amounts incorporated and released were determined using iodine-125 ((125)I) radio-labelled neurotrophins. Neurite outgrowth from cochlear neural explants grown on the conducting polymer was equivalent to that on tissue culture plastic but significantly improved with the incorporation of NT-3 and BDNF. Neurite outgrowth from explants grown on polymers containing both NT-3 and BDNF showed significant improvement over PPy doped only with NT-3, due to the synergistic effect of both neurotrophins. Neurite outgrowth was significantly improved when the polymer containing both neurotrophins was electrically stimulated. It is envisaged that when applied to the cochlear implant, these conducting and novel polymer films will provide a biocompatible substrate for storage and release of neurotrophins to help protect auditory neurons from degradation after sensorineural hearing loss and encourage neurite outgrowth towards the electrodes.
Journal of Controlled Release 09/2009; 141(2):161-7. · 5.73 Impact Factor
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ABSTRACT: A biosynthetic platform composed of a conducting polypyrrole sheet embedded with unidirectional biodegradable polymer fibers is described (see image; scale bar=50 mu m). Such hybrid systems can promote rapid directional nerve growth for neuro-regenerative scaffolds and act as interfaces between the electronic circuitry of medical bionic devices and the nervous system.
Advanced Materials 08/2009; 21(43):4393 - 4397. · 13.88 Impact Factor
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ABSTRACT: Conducting polymers have been developed as substrates for in vitro studies with a range of cell types including electrically-excitable cells such as nerve and smooth muscle. The goal of this study was to optimise and characterise a range of polypyrrole materials to act as substrates for electrical stimulation of differentiating skeletal myoblasts. Although all of the polymer materials provided suitable substrates for myoblast adhesion and proliferation, significant differences became apparent under the low-serum conditions used for differentiation of primary myoblasts. The significance of the work lies in the design and control of polymer materials to facilitate different stages of skeletal muscle cell proliferation and/or differentiation, opening up opportunities for engineering of this tissue. This paper therefore constitutes not just a biocompatibility assessment but a comprehensive study of how synthesis conditions affect the final outcome in terms of cell response.
Biomaterials 08/2009; 30(29):5292-304. · 7.40 Impact Factor
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Rachael T Richardson,
Andrew K Wise,
Brianna C Thompson,
Brianna O Flynn,
Patrick J Atkinson,
Nicole J Fretwell,
James B Fallon,
Gordon G Wallace,
Rob K Shepherd, Graeme M Clark,
Stephen J O'Leary
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ABSTRACT: Sensorineural hearing loss is associated with gradual degeneration of spiral ganglion neurons (SGNs), compromising hearing outcomes with cochlear implant use. Combination of neurotrophin delivery to the cochlea and electrical stimulation from a cochlear implant protects SGNs, prompting research into neurotrophin-eluting polymer electrode coatings. The electrically conducting polypyrrole/para-toluene sulfonate containing neurotrophin-3 (Ppy/pTS/NT3) was applied to 1.7 mm2 cochlear implant electrodes. Ppy/pTS/NT3-coated electrode arrays stored 2 ng NT3 and released 0.1 ng/day with electrical stimulation. Guinea pigs were implanted with Ppy/pTS or Ppy/pTS/NT3 electrode arrays two weeks after deafening via aminoglycosides. The electrodes of a subgroup of these guinea pigs were electrically stimulated for 8 h/day for 2 weeks. There was a loss of SGNs in the implanted cochleae of guinea pigs with Ppy/pTS-coated electrodes indicative of electrode insertion damage. However, guinea pigs implanted with electrically stimulated Ppy/pTS/NT3-coated electrodes had lower electrically-evoked auditory brainstem response thresholds and greater SGN densities in implanted cochleae compared to non-implanted cochleae and compared to animals implanted with Ppy/pTS-coated electrodes (p<0.05). Ppy/pTS/NT3 did not exacerbate fibrous tissue formation and did not affect electrode impedance. Drug-eluting conducting polymer coatings on cochlear implant electrodes present a clinically viable method to promote preservation of SGNs without adversely affecting the function of the cochlear implant.
Biomaterials 01/2009; 30(13):2614-24. · 7.40 Impact Factor
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ABSTRACT: Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over 7 days. A 3-day SGN explant assay found that neurite outgrowth from explants was 12.3-fold greater when polymers contained BDNF (p < 0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge, and act as a substrate for nerve-electrode interactions is discussed for specialized applications such as cochlear implants.
Journal of Biomedical Materials Research Part A 10/2008; 91(1):241-50. · 2.63 Impact Factor
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ABSTRACT: The restoration of hearing to persons with severely or profoundly impaired hearing by means of a cochlear implant is one of the great achievements of bionics applied to medicine. However, pneumococcal meningitis in implant recipients has received high profile public attention as a result of the US Food and Drug Administration's public health notification and recent media attention. Worldwide, 118 of the 60,000 people who received cochlear implants over the past 20 years have acquired meningitis, causing deep concern in the international medical community. This review provides answers to pediatricians, internists, and infectious diseases doctors who have patients with cochlear implants and who have questions about the safety of the cochlear implant from both the clinical and scientific research perspectives. Both clinical and laboratory research support the notion that pneumococcal meningitis is more likely in patients who receive cochlear implantation, and that the surgical insertion technique and the cochlear implant design should be nontraumatic, and that all cochlear implant recipients should be offered vaccination against Streptococcus pneumoniae.
Clinical Infectious Diseases 02/2008; 46(1):e1-7. · 9.15 Impact Factor
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BMJ (Clinical research ed.). 12/2007; 335(7629):1058.
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ABSTRACT: To examine if a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) reduces the risk of meningitis in healthy rats after cochlear implantation.
Interventional animal study.
Thirty-six rats (18 immunized and 18 unimmunized) received cochlear implantations and were then infected with Streptococcus pneumoniae via 3 different routes (hematogenous, middle ear, and inner ear) in numbers sufficient to induce meningitis.
The rats with implants that received PPV23 were protected from meningitis when the bacteria were delivered via the hematogenous and middle-ear routes (Fisher exact test P<.05). However, the protective effect of the vaccine in the rats with implants was only moderate when the bacteria were inoculated directly into the inner ear.
Our animal model clearly demonstrates that immunization can protect healthy rats with a cochlear implant from meningitis caused by a vaccine-covered serotype. This finding supports the notion that all current and future implant recipients should be vaccinated against S pneumoniae.
Archives of Otolaryngology - Head and Neck Surgery 10/2007; 133(10):987-94. · 1.63 Impact Factor
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ABSTRACT: The study goals were to examine whether cochlear implantation increases the risk of meningitis in the absence of other risk factors and to understand the pathogenesis of pneumococcal meningitis post cochlear implantation.
Four weeks following surgery, 54 rats (18 of which received a cochleostomy alone, 18 of which received a cochleostomy and acute cochlear implantation using standard surgical techniques, and 18 of which received a cochlear implant) were infected with Streptococcus pneumoniae via three different routes of bacterial inoculation (middle ear, inner ear, and intraperitoneal) to represent all potential routes of bacterial infection from the upper respiratory tract to the meninges.
The presence of a cochlear implant reduced the threshold of bacteria required to cause pneumococcal meningitis from all routes of infection in healthy animals.
The presence of a cochlear implant increases the risk of pneumococcal meningitis regardless of the route of bacterial infection.
Early detection and treatment of pneumococcal infection such as otitis media may be required, as cochlear implantation may lead to a reduction of infectious threshold for meningitis.
Otolaryngology Head and Neck Surgery 05/2007; 136(4):589-96. · 1.72 Impact Factor
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ABSTRACT: To examine the risk of pneumococcal meningitis in healthy rats that received a severe surgical trauma to the modiolus and osseous spiral lamina or the standard insertion technique for acute cochlear implantation.
Interventional animal studies.
Fifty-four otologically normal adult Hooded-Wistar rats.
Fifty-four rats (18 of which received a cochleostomy alone; 18, a cochleostomy and acute cochlear implantation using standard surgical techniques; and 18, a cochleostomy followed by severe inner ear trauma) were infected 4 weeks after surgery with Streptococcus pneumoniae via 3 different routes (hematogenous, middle ear, and inner ear) to represent all potential routes of bacterial infection from the upper respiratory tract to the meninges in cochlear implant recipients with meningitis.
Severe trauma to the osseous spiral lamina and modiolus increased the risk of pneumococcal meningitis when the bacteria were given via the middle or inner ear (Fisher exact test, P<.05). However, the risk of meningitis did not change when the bacteria were given via the hematogenous route. Acute electrode insertion did not alter the risk of subsequent pneumococcal meningitis for any route of infection.
Severe inner ear surgical trauma to the osseous spiral lamina and modiolus can increase the risk of pneumococcal meningitis. Therefore, every effort should be made to ensure that cochlear implant design and insertion technique cause minimal trauma to the bony structures of the inner ear to reduce the risk of pneumococcal meningitis.
Archives of Otolaryngology - Head and Neck Surgery 03/2007; 133(3):250-9. · 1.63 Impact Factor
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ABSTRACT: A minimal threshold of Streptococcus pneumoniae is required to induce meningitis in healthy animals for intraperitoneal (hematogenous), middle ear, and inner ear inoculations, and this threshold may be altered via recent inner ear surgery.
There has been an increase in the number of reported cases of cochlear implant-related pneumococcal meningitis since 2002. The pathogenesis of pneumococcal meningitis is complex and not completely understood. The bacteria can reach the central nervous system (CNS) from the upper respiratory tract mucosa via either hematogenous route or via the inner ear. The establishment of a threshold model for all potential routes of infection to the CNS in animals without cochlear implantation is an important first step to help us understand the pathogenesis of the disease in animals with cochlear implantation.
Fifty-four otologically normal adult Hooded Wistar rats (27 receiving cochleostomy and 27 controls) were inoculated with different amounts of bacterial counts via three different routes (intraperitoneal, middle ear, and inner ear). Rats were monitored during 5 days for signs of meningitis. Blood, cerebrospinal fluid, and middle ear swabs were taken for bacterial culture, and brains and cochleae were examined for signs of infection.
The threshold of bacterial counts required to induce meningitis is lowest in rats receiving direct inner ear inoculation compared with both intraperitoneal and middle ear inoculation. There is no change in threshold between the group of rats with cochleostomy and the control (Fisher's exact test, p < 0.05).
A minimal threshold of bacteria is required to induce meningitis in healthy animals and is different for three different routes of infection (intraperitoneal, middle ear, and inner ear). Cochleostomy performed 4 weeks before the inoculation did not reduce the threshold of bacteria required for meningitis in all three infectious routes. This threshold model will also serve as a valuable tool, assisting clinicians to quantitatively analyze if the presence of a cochlear implant or other CNS prostheses alter the risk of meningitis.
Ontology & Neurotology 01/2007; 27(8):1152-61. · 1.90 Impact Factor
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ABSTRACT: To determine whether ciprofloxacin retains its antimicrobial activity after storage with Healon at ambient temperature and at 37 degrees C over 5 weeks and then to establish whether the application of ciprofloxacin/Healon onto scala tympani electrode arrays reduces the risk of meningitis in implanted rats inoculated with S. pneumoniae.
In vitro laboratory and in vivo animal studies
The antibacterial activity of three concentrations of ciprofloxacin/Healon (7.5, 75, and 750 microg/mL) was examined over 5 weeks at both ambient temperature (23 degrees C) and body temperature (37 degrees C). Thirty-six rats (18 implanted with ciprofloxacin [750 mg/mL]/Healon-coated electrode array and 18 without the coating) were infected with S. pneumoniae 4 weeks after implantation by way of three different routes of infection (hematogenous, middle ear, and inner ear) and observed for the development of meningitis.
The antibacterial activity of ciprofloxacin/Healon was maintained over 5 weeks at both 23 degrees C and 37 degrees C. The implanted rats with the ciprofloxacin/Healon-coated electrode array were protected from meningitis when the bacteria were given by way of the hematogenous route (Fisher's exact test, P = .008) but not when the bacteria were inoculated directly into the middle or inner ear. However, the time to develop meningitis was significantly longer in rats implanted with a coated array, irrespective of the route of inoculation (P < .05, log rank test).
Our animal model demonstrated that a ciprofloxacin-coated electrode array can protect healthy implanted rats from meningitis when the route of infection is hematogenous and can delay the onset of meningitis when bacteria are inoculated directly into the middle or inner ear.
The Laryngoscope 01/2007; 116(12):2138-44. · 1.75 Impact Factor
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ABSTRACT: In this study, a neurotrophin delivery system based on an inherently conducting polymer (ICP) has been developed. Direct incorporation of neurotrophin-3 (NT-3) was investigated and controlled release was tested under various electrochemical conditions. The loading capacity and amount of NT-3 released from the polymer was determined using (125)I-labelled NT-3. Electrochemical stimulation of polypyrrole by pulsed voltage, pulsed current or cyclic voltammetry promoted the release of NT-3 at a greater rate than natural diffusion of NT-3. NT-3 was released from polypyrrole as an initial burst in the first 24 h followed by prolonged release over a subsequent 6 days of sampling. The amount of NT-3 incorporated into the polymer could be controlled by varying the polymerisation time, with longer growth periods incorporating more NT-3. The NT-3 release results indicated that the polymers grown for longer released a lower percentage of the incorporated NT-3 compared to the polymers grown for shorter times. Polymer-based neurotrophin delivery systems have the potential to be incorporated into future treatments for nerve injuries to prevent nerve degradation and promote nerve protection.
Journal of Controlled Release 01/2007; 116(3):285-94. · 5.73 Impact Factor
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ABSTRACT: The rat is a suitable animal to establish a model for the study of pneumococcal meningitis postcochlear implantation.
There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis postimplantation and are based on relatively small animal numbers, making it difficult to assess the cause-and-effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant.
Eighteen nonimplanted rats were infected with 1 x 10 and 1 x 10 colony-forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear, and i.p.) to examine for evidence of meningitis during 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 x 10 CFU i.p., 3 x 10 CFU middle ear, and 1 x 10 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. The histological pattern of cochlear infections for each of the three different inoculating routes were examined.
Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system via either the cochlear aqueduct or canaliculi perforantes of the osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent, and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal meningitis observed in 18 nonimplanted rats inoculated at a lower concentration of S. pneumoniae when observed for 24 hours postinoculation.
Meningitis in implanted rats after inoculation with a clinical isolate of S. pneumoniae is possible via all three potential routes of infection via the upper respiratory tract. The lack of meningitis observed in the 18 nonimplanted rats suggests that longer postinoculation monitoring periods are required to ensure whether or not meningitis will develop. Based on this work, we have developed a new animal model that will allow quantitative risk assessment of meningitis postcochlear implantation, and the assessment of the efficacy of potential interventional strategies in future studies.
Ontology & Neurotology 10/2006; 27(6):844-54. · 1.90 Impact Factor
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ABSTRACT: Ventral cochlear nucleus stellate cells respond to characteristic frequency (CF) tones with sustained (C(S)), transient (C(T)) or onset chopping (O(C)) activity. The mechanisms underlying these different response patterns are not fully understood, and the present study used in vivo intracellular recordings (n = 42) in urethane-anaesthetized rats to examine the possible influence of inhibition on action potential regularity. Hyperpolarization following the offset of a CF tone burst was used as a measure of on-CF inhibition. A cluster analysis based on several membrane potential features, including on-CF inhibition, discriminated three groups in addition to the C(S) response type - two types of C(T) responses and the O(C) type. The different patterns of firing regularity exhibited by C(S/T) neurons reflected different thresholds or degrees of overlap between these cells' narrowly tuned excitatory and inhibitory inputs. C(T) cells with closely matched inhibitory and excitatory response areas showed substantial on-CF inhibition and the greatest decline in firing regularity during a CF tone, whereas those with a mismatch between their response areas showed lateral inhibition and a less marked decline in firing regularity. The presence of inhibition in C(S) neurons did not alter their firing regularity, possibly because of the lower threshold for excitation compared with inhibition. The latency, duration and frequency extent of sustained hyperpolarization in C(S/T) cells is inconsistent with the response properties of O(C) neurons, suggesting that another source(s) of inhibition influences firing regularity, and presumably response magnitude, in these neurons.
European Journal of Neuroscience 04/2005; 21(5):1236-48. · 3.63 Impact Factor
