Intracellular features predicted by extracellular recordings in the hippocampus in vivo.
(49/816)
Multichannel tetrode array recording in awake behaving animals provides a powerful method to record the activity of large numbers of neurons. The power of this method could be extended if further information concerning the intracellular state of the neurons could be extracted from the extracellularly recorded signals. Toward this end, we have simultaneously recorded intracellular and extracellular signals from hippocampal CA1 pyramidal cells and interneurons in the anesthetized rat. We found that several intracellular parameters can be deduced from extracellular spike waveforms. The width of the intracellular action potential is defined precisely by distinct points on the extracellular spike. Amplitude changes of the intracellular action potential are reflected by changes in the amplitude of the initial negative phase of the extracellular spike, and these amplitude changes are dependent on the state of the network. In addition, intracellular recordings from dendrites with simultaneous extracellular recordings from the soma indicate that, on average, action potentials are initiated in the perisomatic region and propagate to the dendrites at 1.68 m/s. Finally we determined that a tetrode in hippocampal area CA1 theoretically should be able to record electrical signals from approximately 1, 000 neurons. Of these, 60-100 neurons should generate spikes of sufficient amplitude to be detectable from the noise and to allow for their separation using current spatial clustering methods. This theoretical maximum is in contrast to the approximately six units that are usually detected per tetrode. From this, we conclude that a large percentage of hippocampal CA1 pyramidal cells are silent in any given behavioral condition. (+info)
Differential cardiorespiratory control elicited by activation of ventral medullary sites in mice.
(50/816)
We studied the respiratory and blood pressure responses to chemical stimulation of two regions of the ventral brainstem in mice: the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). Stimulation of the RVLM by microinjections of the excitatory amino acid L-glutamate induced increases in diaphragm activity and breathing frequency, elevation of blood pressure (BP), and a slight increase in heart rate (HR). However, activation of the CVLM induced a decrease in breathing frequency, mainly due to prolongation of expiratory time (TE), and hypotension associated with a slight slowing of HR. Because adrenergic mechanisms are known to participate in the control of respiratory timing, we examined the role of alpha(2)-adrenergic receptors in the RVLM region in mediating these inhibitory effects. The findings demonstrated that blockade of the alpha(2)-adrenergic receptors within the RVLM by prior microinjection of SKF-86466 (an alpha(2)-adrenergic receptor blocker) significantly reduced changes in TE induced by CVLM stimulation but had little effect on BP responses. These results indicate that, in mice, activation of the RVLM increases respiratory drive associated with an elevation of BP, but stimulation of CVLM induces prolongation of TE via an alpha(2)-adrenergic signal transduction pathway. (+info)
Exercise in the heat is limited by a critical internal temperature.
(51/816)
We examined whether fatigue during exertional heat stress occurred at a critical internal temperature independent of the initial temperature at the start of exercise. Microwaves (2.1 GHz; 100 mW/cm(2)) were used to rapidly (3-8 min) heat rats before treadmill exercise to exhaustion. In a repeated-measures design, food-restricted male Sprague-Dawley rats (n = 11) were preheated to three levels (low, medium, and high). In addition, two sham exposures, Sham 1 and Sham 2, were administered at the beginning and end of the study, respectively. At the initiation of exercise, hypothalamic (T(hyp)) and rectal (T(rec)) temperatures ranged from 39.0 degrees C to 42.8 degrees C (T(hyp)) and 42.1 degrees C (T(rec)). The treadmill speed was 17 m/min (8 degrees grade), and the ambient temperature during exercise was 35 degrees C. Each treatment was separated by 3 wk. Run time to exhaustion was significantly reduced after preheating. There was a significant negative correlation between run time and initial T(hyp) and T(rec) (r = 0.73 and 0.74, respectively). The temperatures at exhaustion were not significantly different across treatments, with a range of 41.9-42.2 degrees C (T(hyp)) and 42.2-42.5 degrees C (T(rec)). There were no significant differences in run time in the sham runs administered at the start and end of the investigation. No rats died as a result of exposure to any of the treatments, and body weight the day after each treatment was unaffected. These results support the concept that a critical temperature exists that limits exercise in the heat. (+info)
Efficient inhibition of in vivo human malignant glioma growth and angiogenesis by interferon-beta treatment at early stage of tumor development.
(52/816)
Malignant gliomas are highly angiogenic and aggressive tumors. IFN-beta has been used for the treatment of patients with malignant glioma; however, its antitumor mechanism in vivo remains unclear. To understand the in vivo antitumor effect and mechanism of recombinant human IFN-beta (rhIFN-beta) depending on the stages of tumor development or progression, we used orthotopic xenograft brain tumors generated by stereotactic intracerebral implantation of U-87 human glioma cells in nude mice. Mice bearing tumors 7 days (group 1) and 21 days (group 2) postimplant were treated with 2 x 10(5) IU/day of rhIFN-beta or saline i.p. for 15 days, respectively. Tumor growth was suppressed by 69.6% in group 1 and 10.8% in group 2 compared with tumors of each control group treated with saline. rhIFN-beta-treated group 1 animals showed 38% reduction in vascularization along with a 2.5-fold increase of the apoptotic index and no change in the proliferative index as compared with untreated tumors. The expression level of vascular endothelial cell growth factor and basic fibroblast growth factor was not affected by rhIFN-beta treatment. rhIFN-beta showed inhibitory activity on proliferation of U-87 cells, human umbilical vein endothelial cells, and PAM 212 murine keratinocytes in vitro. Our results indicate that the in vivo antitumor effect of rhIFN-beta on malignant gliomas may be mediated, at least in part, via angiogenesis inhibition rather than antiproliferative activity and that rhIFN-beta may be more effective for the treatment of malignant glioma patients at an early stage with minimal or microscopic tumor burdens rather than at an advanced stage of tumor development. (+info)
Studies on the mechanism controlling growth hormone release induced by chlorpromazine in the anesthetized rat.
(53/816)
In intact urethane-anesthetized rats, plasma growth hormone (GH) levels were low but increased significantly following intravenous injection of chlorpromazine. Plasma GH levels were significantly elevated in rats with hypothalamic cuts such as complete deafferentiation, anterior cut and antero-lateral cut, whereas plasma GH levels in rats with posterior cut or postero-lateral cut were not significantly different from those in rats with sham-operation. Intravenous injection of chlorpromazine caused an increase of plasma GH in rats with any type of hypothalamic cut. However, the maximum increments of plasma GH following chlorpromazine were larger in rats with antero-lateral cut and smaller in rats with posterior cut than in rats with sham-operation. These results suggest that extrahypothalamic inhibiting and stimulating neurons influence the regulatory mechanism of rat GH secretion through anterior and posterior routes to the hypothalamus respectively. (+info)
Ionic mechanism of the efferent olivo-cochlear inhibition studied by cochlear perfusion in the cat.
(54/816)
1. A method for perfusing the scala tympani of the cat's cochlea from basal turn to apex is described. The perfusion with modified Krebs solution did not interfere with the recording of cochlear microphonic (CM) and neural responses to sound, nor with the efferent inhibition elicited by stereotaxic stimulation of the crossed olivo-cochlear bundle (COCB) in the medulla. 2. Cochlear perfusion with solutions in which most of the chloride was replaced by large anions (sulphate or gluconate) decreased or eliminated auditory nerve or the ventral cochlear nucleus. These effects were reversible. They were only observed if the rate of perfusion (2-20 mul/min) was adequate to reduce the chloride concentration in perilymph below about 80 mM, this being estimated, in different perfusion of the same cochlea, by a chloride-selective electrode. 3. The COCB-induced negative shift of the endocochlear potential recorded with a glass micro-electrode inserted into the scala media was abolished by I.V. strychnine o.2 mg/kg. It was decreased when the perilymph chloride was reduced to 50-70 mM and could be abolished when the perilymph chloride dropped to about 5 mM. 4. The COCB-induced potentiation of the cochlear microphonic potential was also reduced by chloride substitution but the pattern of this effect differed from that of neural inhibition. 5. Similar cochlear perfusions with a solution in which the small diameter bromide anion was substituted for chloride did not affect the COCB-efferent effects. 6. The data indicate that the inhibitory transmitter released by COCB terminals elicits an increased conductance to small anions (normally to chloride) in the membrane of the auditory dendrite and of the outer hair cell. The significance of the COCB-induced negative shift of endocochlear potential and of the potentiation of CM is discussed, as well as the pre- and post-synaptic mechanisms involved in the efferent gating exerted on the auditory input. The latter would seem to involve primarily a post-synaptic mechanism at efferent axo-dendritic synapses. (+info)
Stereotactic core-needle breast biopsy by surgeons: minimum 2-year follow-up of benign lesions.
(55/816)
OBJECTIVE: To evaluate the reliability of stereotactic core-needle breast biopsy (SCNB) performed by surgeons to detect histologically benign tissue. SUMMARY BACKGROUND DATA: Stereotactic core-needle breast biopsy is widely used to obtain tissue for definitive pathologic diagnosis of mammographically suspicious breast lesions. It has an incidence of malignancy detection similar to that of open biopsy. The potential for sampling error is a concern. Minimal data regarding follow-up and failure rate are available, especially from series performed exclusively by surgeons. METHODS: Pertinent medical records of all patients who underwent SCNB between April 1995 and October 1997 were reviewed. Breast lesions were classified by mammographic Breast Imaging-Reporting and Data Systems (BI-RADS) categories before SCNB. Benign biopsy specimens were classified as nonproliferative or proliferative. Malignant lesions and those with atypical histopathology by SCNB were excluded from this analysis. All lesions initially reported as benign were followed up mammographically for at least 2 years for any suspicious change requiring repeat biopsy. RESULTS: During the 31-month period, SCNB was performed on 694 lesions in 619 patients. Histologic evidence of malignancy was found in 112 lesions (16%). The initial histologic diagnosis for the remaining 582 lesions was benign. Four hundred lesions were available for follow-up; of these, 373 (93%) were mammographically categorized as BI-RADS 3 (probably benign) or 4 (suspicious). Three hundred forty-three lesions were categorized as nonproliferative and 151 as proliferative (94 had combined nonproliferative and proliferative histology). Follow-up ranged from 24 to 48 months (mean 33 months). During the follow-up period, 87 lesions (21.8%) underwent either image-guided or open biopsy. At the time of follow-up rebiopsy, ductal carcinoma in situ was found in four lesions and infiltrating ductal carcinoma was found in one, for an overall false-negative rate of 4.3% (5/117) and a negative predictive value of 98.8% (395/400). For the five false-negative cases, the interval from initial SCNB to definitive diagnosis ranged from 7 to 36 months. No correlation was found between the type of initial histopathology and development of malignancy. CONCLUSIONS: These results support SCNB as an alternative to open biopsy and show the reliability of SCNB when benign pathology is obtained. However, given the possibility of sampling error and the nature of breast disease, close mammographic and clinical follow-up is necessary. The false-negative rate and negative predictive value in this series compare favorably with those in other reports, supporting the fact that surgeons can confidently use SCNB in the evaluation and treatment of breast disease. (+info)
Somnolence, akinesia, and sensory activation of motivated behavior in the lateral hypothalamic syndrome.
(56/816)
After lateral hypothalamic damage in rats, somnolence, akinesia, and sensory neglect combine to produce complete aphagia. Only simple automatisms (such as grooming, chewing, licking) are present, but intense stimuli can activate more complex actions (walking, orientation, swimming). In the anorexic stage, tactile stimuli dominate in steering locomotion and "spontaneous" locomotion depends on activation from the empty stomach. (+info)