Journal of Physiology
Công bố khoa học tiêu biểu
Sắp xếp:
Synaptic dynamics control the timing of neuronal excitation in the activated neocortical microcircuit It is well established that sensory stimulation results in the activity of multiple functional columns in the neocortex. The manner in which neurones within each column are active in relation to each other is, however, not known. Multiple whole‐cell recordings in activated neocortical slices from rat revealed diverse correlation profiles of excitatory synaptic input to different types of neurones. The specific correlation profile between any two neurones could be predicted by the settings of synaptic depression and facilitation at the input synapses. Simulations further showed that patterned activity is essential for synaptic dynamics to impose the temporal dispersion of excitatory input. We propose that synaptic dynamics choreograph neuronal activity within the neocortical microcircuit in a context‐dependent manner.
Journal of Physiology - Tập 556 Số 1 - Trang 19-27 - 2004
Gastric vagal afferent modulation by leptin is influenced by food intake status Key points
Obesity occurs when energy intake exceeds expenditure, and the excess energy is stored as fat. We show that, after a 14 h food deprivation or 12 weeks consumption of a high‐fat diet, gastric vagal afferent responses to mechanical stimulation in the presence of the satiety peptide leptin are altered. Leptin has an excitatory effect on gastric mucosal vagal afferents, which is abolished after food restriction or prolonged excess. In contrast, leptin has an inhibitory effect on gastric tension‐sensitive afferents, but only after food restriction or energy excess conditions. These changes in the response to leptin in the stomach, after food restriction or prolonged high‐fat feeding, occur in such a manner as to facilitate an increase in food intake in both conditions. Abstract Energy intake is strongly influenced by vagal afferent signals from the stomach, and is also modulated by leptin. Leptin may be secreted from gastric epithelial cells, so we aimed to determine the direct effect of leptin on gastric vagal afferents under different feeding conditions. Female C57BL/6 mice were fed standard laboratory diet, high‐fat diet or were food restricted. The expression of leptin receptor (Lep‐R) and its signal transduction molecules in vagal afferents was determined by retrograde tracing and reverse‐transcription polymerase chain reaction, and the relationship between leptin‐immunopositive cells and gastric vagal afferent endings determined by anterograde tracing and leptin immunohistochemistry. An in vitro preparation was used to determine the functional effects of leptin on gastric vagal afferents and the second messenger pathways involved. Leptin potentiated vagal mucosal afferent responses to tactile stimuli, and epithelial cells expressing leptin were found close to vagal mucosal endings. After fasting or diet‐induced obesity, potentiation of mucosal afferents by leptin was lost and Lep‐R expression reduced in the cell bodies of gastric mucosal afferents. These effects in diet‐induced obese mice were accompanied by a reduction in anatomical vagal innervation of the gastric mucosa. In striking contrast, after fasting or diet‐induced obesity, leptin actually inhibited responses to distension in tension receptors. The inhibitory effect on gastric tension receptors was mediated through phosphatidylinositol 3‐kinase‐dependent activation of large‐conductance calcium‐activated potassium channels. The excitatory effect of leptin on gastric mucosal vagal afferents was mediated by phospholipase C‐dependent activation of canonical transient receptor potential channels. These data suggest the effect of leptin on gastric vagal afferent excitability is dynamic and related to the feeding state. Paradoxically, in obesity, leptin may reduce responses to gastric distension following food intake.
Journal of Physiology - Tập 591 Số 7 - Trang 1921-1934 - 2013
Responses of the pyramidal tract to stimulation of the baboon's motor cortex 1. The arm area of the baboon's precentral motor cortex was stimulated by brief surface‐anodal pulses, and the discharge of the corticospinal tract (the ‘pyramidal tract waves’) was recorded by an electrode resting on the dorsolateral surface of the cervical spinal cord. 2. Some properties of the pyramidal tract waves were described, and they were also studied in relation to the firing of single cortico spinal fibres. 3. The results led to the conclusion that the later pyramidal tract waves (the ‘I waves’) were almost exclusively due to a semi‐synchronous repetitive discharge of the same fast cortico spinal fibres as those responsible for the initial wave (the ‘D wave’). 4. Some problems concerning the origin and significance of the I waves were discussed.
Journal of Physiology - Tập 191 Số 3 - Trang 653-672 - 1967
Electric and magnetic stimulation of human motor cortex: surface EMG and single motor unit responses. 1. The effects of different forms of brain stimulation on the discharge pattern of single motor units were examined using the post‐stimulus time histogram (PSTH) technique and by recording the compound surface electromyographic (EMG) responses in the first dorsal interosseous (FDI) muscle. Electrical and magnetic methods were used to stimulate the brain through the intact scalp of seven normal subjects. Electrical stimuli were applied either with the anode over the lateral central scalp and the cathode at the vertex (anodal stimulation) or with the anode at the vertex and the cathode lateral (cathodal stimulation). Magnetic stimulation used a 9 cm diameter coil centred at the vertex; current in the coil flowed either clockwise or anticlockwise when viewed from above. 2. Supramotor threshold stimuli produced one or more narrow (less than 2 ms) peaks of increased firing in the PSTH of all thirty‐two units studied. Anodal stimulation always produced an early peak. The latencies of the peaks produced by other forms of stimulation, or by high intensities of anodal stimulation, were grouped into four time bands relative to this early peak, at intervals of ‐0.5 to 0.5, 1‐2, 2.5‐3.5 and 4‐5.5 ms later. Peaks occurring within these intervals are referred to as P0 (the earliest anodal), P1, P2 and P3 respectively. 3. At threshold, anodal stimulation evoked only the P0 peak; at higher intensities, the P2 or more commonly the P3 peak also was recruited. The size of the P0 peak appeared to saturate at high intensities. 4. In five of six subjects, cathodal stimulation behaved like anodal stimulation, except that there was a lower threshold for recruitment of the P2 or P3 peak relative to that of the P0 peak. In the other subject, the P3 peak was recruited before the P0 peak. 5. Anticlockwise magnetic [corrected] stimulation, at threshold, often produced several peaks. These always included a P1 peak, and usually a P3 peak. A P0 peak in the PSTH was never produced by an anticlockwise stimulation [corrected] at intensities which we could explore with the technique. 6. Clockwise magnetic [corrected] stimulation never recruited a P1 peak; in most subjects a P3 peak was recruited first and at higher intensities was accompanied by P0 or P2 peaks. 7. On most occasions when more than one peak was observed in a PSTH, the unit fired in only one of the preferred intervals after each shock. However, double firing was seen in five units when high intensities of stimulation were used.(ABSTRACT TRUNCATED AT 400 WORDS)
Journal of Physiology - Tập 412 Số 1 - Trang 449-473 - 1989
The mode of activation of pyramidal tract cells by intracortical stimuli. 1. Direct and indirect effects of intracortical stimulattion on pyramidal tract cells were compared in the monkey and in the cat under barbiturate or chloralose anaesthesia. The hind‐limb motor areas were explored, that in the monkey only within the convex part of the precentral gyrus. The intracortical stimuli were applied in the nearest vicinity of pyramidal tract cells, where antidromic spike potentials of single cells were recorded. 2. Average records of descending volleys in corticospinal tract fibres were taken from the surface of the lateral funiculus or from its dissected fascicles. The sensitivity of the recording was sufficient to detect responses in single fibres. 3. The latencies of the earliest descending volleys evoked by weak intracortical stimuli were compared with the latencies of the antidromic spike potentials of pyramidal tract cells evoked by stimulation of the lateral funiculus at a low lumbar level (same conduction distance). Only in about one third of cases these latencies were similar and compatible with a direct activation of pyramidal tract cells. In the remaining cases they indicated mono‐ or polysynaptic activation of pyramidal tract cells. 4. Latencies of the later components of the descending volleys indicated that they were due to indirect activation of pyramidal tract cells in practically all cases. 5. The components of the descending volleys attributable to the indirect activation of pyramidal tract cells were greatly increased when repetitive intracortical stimuli were applied instead of single ones. 6. The investigation leads to the conclusion that a weak intracortical stimulation is relatively ineffective in a direct excitation of pyramidal tract cells and that the effects of such a stimulation are mainly indirect, especially when repetitive stimuli are used.
Journal of Physiology - Tập 249 Số 3 - Trang 617-636 - 1975
Post‐synaptic effects of cortical stimulation on forelimb motoneurones in the baboon 1. The arm area of the baboon's precentral motor cortex was stimulated by brief surface‐anodal pulses, and the post‐synaptic potentials elicited in contralateral forelimb motoneurones were studied by intracellular recording. 2. Strong cortical stimuli elicited a rapid series of excitatory and, in some cells, inhibitory post‐synaptic potentials (EPSPs and IPSPs respectively). Comparisons with the simultaneously recorded response of the pyramidal tract indicated that these post‐synaptic potentials were due to a repetitive discharge of fast pyramidal fibres. Thus, the later synaptic events were mostly due to a repetition of the early monosynaptic EPSP and early IPSP respectively. 3. Inhibition was seen more often in cells whose monosynaptic EPSP had a small maximal size than in those whose monosynaptic EPSP was larger. The net depolarization produced by a strong cortical stimulus was related to the maximal size of the early monosynaptic EPSP. 4. In the Discussion, an interpretation is suggested for previous findings concerning the spinal distribution of late synaptic effects elicited by cortical stimulation.
Journal of Physiology - Tập 191 Số 3 - Trang 673-690 - 1967
Control of water content of non‐metabolizing kidney slices by sodium chloride and polyethylene glycol (Peg 6000) 1. Cortical slices from kidneys of adult rats were equilibrated for 24 and 48 hr in the refrigerator in solutions containing 5 m
M ‐K, 2·5 m
M ‐Ca and Mg,
M /15 phosphate buffer (pH 7·4), 5 m
M cyanide and iodoacetate with 5, 6, 7 and 8% polyethylene glycol (PEG 6000) and 77, 154, 308, 462 and 770 m
M ‐NaCl. 2. There were no consistent differences in water content between slices after 24 and after 48 hr. 3. Slices contained more water when either the concentration of NaCl or that of PEG was reduced. The increase in water content induced by lowering the concentration of either was prevented by a higher concentration of the other. 4. Water content was held constant at 3·25 kg.kg−1 dry PEG‐free tissue despite a fall in [NaCl] from 770 to 77 m
M (more than 1200 m‐osmole.kg−1 ) by increasing PEG from 5·1 to 7·7% corresponding to an increase of the order of 15 m‐osmole.kg−1 . 5. It is suggested that PEG 6000 was so much more effective than NaCl, osmole for osmole, because PEG 6000 acted as a non‐penetrating solute, whereas NaCl penetrated the slices and reduced the ‘Donnan excess’ component of the intracellular colloid osmotic pressure so that this could be balanced by a smaller concentration of PEG.
Journal of Physiology - Tập 213 Số 1 - Trang 227-234 - 1971
Aquaporin water channels – from atomic structure to clinical medicine The water permeability of biological membranes has been a longstanding problem in physiology, but the proteins responsible for this remained unknown until discovery of the aquaporin 1 (AQP1) water channel protein. AQP1 is selectively permeated by water driven by osmotic gradients. The atomic structure of human AQP1 has recently been defined. Each subunit of the tetramer contains an individual aqueous pore that permits single‐file passage of water molecules but interrupts the hydrogen bonding needed for passage of protons. At least 10 mammalian aquaporins have been identified, and these are selectively permeated by water (aquaporins) or water plus glycerol (aquaglyceroporins). The sites of expression coincide closely with the clinical phenotypes ‐ ranging from congenital cataracts to nephrogenic diabetes insipidus. More than 200 members of the aquaporin family have been found in plants, microbials, invertebrates and vertebrates, and their importance to the physiology of these organisms is being uncovered.
Journal of Physiology - Tập 542 Số 1 - Trang 3-16 - 2002
Interpretation of light diffraction by cross‐striated muscle as Bragg reflexion of light by the lattice of contractile proteins. 1. The diffraction spectrum obtained by illuminating a cross‐striated muscle fibre with a narrow beam of monochromatic light generally shows asymmetry of light intensity between left and right spectral lines. 2. The asymmetry of light intensity in left and right spectral lines is reversed when the fibre is rotated by 180 degrees. This indicates that intensities of the spectral lines are determined more by Bragg reflexion than by simple diffraction as in a plane grating. Populations of myofibrils with differing tilt of lattice planes must exist in each illuminated fibre segment to account for simultaneous Bragg reflexion to the left‐ and right‐hand sides. 3. The light intensity of spectral lines shows a complicated dependence on the angle at which the incident beam is directed against the fibre. This 'intensity distribution' seems to reflect the specific myofibrillar arrangement at the site of illumination. 4. The intensity distributions of the left and right first order lines show close correlation if the deflexion of the incident beam differs by twice the Bragg angle. 5. The deflexion angle of the incident beam at which maximum intensity in spectral lines is obtained depends on sarcomere length as predicted by Bragg's formula. 6. Intensities of the first and second order lines are little correlated when recorded at the same beam deflexion, but are well correlated when recorded at beam deflexions calculated from Bragg's formula. 7. When a diffraction line is scanned perpendicularly to the meridional plane, the light intensity shows fluctuations resembling those obtained by beam deflexion within the meridional plane.
Journal of Physiology - Tập 290 Số 2 - Trang 317-330 - 1979
Dissociations between behavioural recovery and restoration of vestibular activity in the unilabyrinthectomized guinea‐pig. 1. In the guinea‐pig, a unilateral labyrinthectomy induces postural disturbances and an ocular nystagmus which abate or disappear over time. These behavioural changes are accompanied by an initial collapse and a subsequent restoration of the spontaneous activity in the neurones of the ipsilateral vestibular nuclei. Recently, it has been shown that the vestibular neuronal activity remained collapsed over at least 10 h whereas its restoration was complete 1 week after the lesion. The aims of this study were to determine when restoration of spontaneous activity in the partially deafferented vestibular neurones started and to compare the time courses of the behavioural and neuronal recoveries in guinea‐pigs that had undergone a unilateral labyrinthectomy. 2. Neuronal discharge measurements were made using chronic extracellular recording of single unit activity. After a left labyrinthectomy, electrodes, were placed on the site of the destroyed labyrinth to enable stimulation of the left vestibular nerve. Behavioural measurements included chronic recording of eye movements by the scleral search coli technique. After a left labyrinthectomy, lateral deviation of the head, twisting of the head, and eye velocity of the slow phases of the nystagmus were measured. 3. The neuronal activity of the rostral part of the vestibular nuclear complex on the lesioned side was recorded in alert guinea‐pigs over 4 h recording sessions between 12 and 72 h after the lesion. 4. The criterion used to select vestibular neurones for analysis was their recruitment by an electric shock on the vestibular nerve. In addition, in order to explore a uniform population, we focused on neurones recruited at monosynaptic latencies (0.85‐1.15 ms). 5. For each recording period, the mean resting rate was calculated animal by animal and the grand mean of these individual resting rate means was calculated. Previously, a decline in the grand mean resting rate from 35.8 +/‐ 6.0 spikes s‐1 (control state) to 7.1 +/‐ 4.2 spikes s‐1 during the first 4 h after labyrinthectomy has been shown. In the present study, the first sign of recovery was observed during the 12‐16 h recording period when the resting rate grand mean increased to 16.3 +/‐ 3.9 spikes s‐1. This grand mean activity did not change significantly during the following 12 h. Thereafter, restoration of neuronal activity improved and was complete 1 week after the lesion. 6. Although the abatement of the vestibular symptoms roughly paralleled the restoration of neuronal activity in the vestibular nuclei, some discrepancies between the time courses of both phenomena emerged. An important step in postural recovery (the animals managed to stand up) and a major part of the abatement of the nystagmus occurred before the recovery of vestibular neuronal activity. In addition, lateral deviation of the head disappeared while restoration of the neuronal activity was incomplete, but significant head twisting was still evident when vestibular resting rates had recovered completely. 7. We conclude that restoration of neuronal activity in the ipsilateral vestibular nuclei starts 12 h after the lesion and that restoration of neuronal activity in the ipsilateral vestibular nuclei is not the only mechanism underlying behavioural vestibular compensation.
Journal of Physiology - Tập 500 Số 2 - Trang 509-522 - 1997
Tổng số: 803
- 1
- 2
- 3
- 4
- 5
- 6
- 81