Cracking the neuronal code.
Explore the source record for details and available documents.
Action Potentials↗
Biomedical subjects
N Spruston
Publications and source records attributed to N Spruston.
Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites.
The temporal and spatial profile of activity-evoked changes in membrane potential and intracellular calcium concentration in the dendrites of hippocampal CA1 pyramidal neurons was examined with simultaneous somatic and dendritic patch-pipette recording and calcium imaging experiments. Action potentials are initiated close to the soma of these neurons and backpropagate into the dendrites in an activity-dependent manner; those occurring early in a train propagate actively, whereas those occurring later fail to actively invade the distal dendrites. Consistent with this finding, dendritic calcium transients evoked by single action potentials do not significantly attenuate with distance from the soma, whereas those evoked by trains attenuate substantially. Failure of action potential propagation into the distal dendrites often occurs at branch points. Consequently, neighboring regions of the dendritic tree can experience different voltage and calcium signals during repetitive action potential firing. The influence of backpropagating action potentials on synaptic integration and plasticity will therefore depend on both the extent of dendritic branching and the pattern of neuronal activity.
Action Potentials↗
Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons.
1. Properties of dendritic glutamate receptor (GluR) channels were investigated using fast application of glutamate to outside-out membrane patches isolated from the apical dendrites of CA3 and CA1 pyramidal neurons in rat hippocampal slices. CA3 patches were formed (15-76 microns from the soma) in the region of mossy fibre (MF) synapses, and CA1 patches (25-174 microns from the soma) in the region of Schaffer collateral (SC) innervation. 2. Dual-component responses consisting of a rapidly rising and decaying component followed by a second, substantially slower, component were elicited by 1 ms pulses of 1 mM glutamate in the presence of 10 microM glycine and absence of external Mg2+. The fast component was selectively blocked by 2-5 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the slow component by 30 microM D-2-amino-5-phosphonopentanoic acid (D-AP5), suggesting that the fast and slow components were mediated by the GluR channels of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and NMDA type, respectively. The peak amplitude ratio of the NMDA to AMPA receptor-mediated components varied between 0.03 and 0.62 in patches from both CA3 and CA1 dendrites. Patches lacking either component were rarely observed. 3. The peak current-voltage (I-V) relationship of the fast component was almost linear, whereas the I-V relationship of the slow component showed a region of negative slope in the presence of 1 mM external Mg2+. The reversal potential for both components was close to 0 mV. 4. Kainate-preferring GluR channels did not contribute appreciably to the response to glutamate. The responses to 100 ms pulses of 1 mM glutamate were mimicked by application of 1 mM AMPA, whereas 1 mM kainate produced much smaller, weakly desensitizing currents. This suggests that the fast component is primarily mediated by the action of glutamate on AMPA-preferring receptors. 5. The mean elementary conductance of AMPA receptor channels was about 10 pS, as estimated by non-stationary fluctuation analysis. The permeability of these channels to Ca2+ was low (approximately 5% of the permeability to Cs+). 6. The elementary conductance of NMDA receptor channels was larger, with a main conductance state of about 45 pS. These channels were 3.6 times more permeable to Ca2+ than to Cs+.(ABSTRACT TRUNCATED AT 400 WORDS)
2-Amino-5-phosphonovalerate↗
Probing dendritic function with patch pipettes.
Most neurons in the CNS have complex, branching dendritic trees, which receive the majority of all synaptic input. As it is difficult to make electrical recordings from dendrites because of their small size, most of what is known about their electrical properties has been inferred from recordings made at the soma. By taking advantage of the higher resolution offered by improved optics, it is now possible to make patch-pipette recordings from the dendrites of neurons in brain slices under visual control. This new technique promises to provide valuable new information concerning dendritic function.
Animals↗
Dendritic attenuation of synaptic potentials and currents: the role of passive membrane properties.
The dendritic trees of neurons are structurally and functionally complex integrative units receiving thousands of synaptic inputs that have excitatory and inhibitory, fast and slow, and electrical and biochemical effects. The pattern of activation of these synaptic inputs determines if the neuron will fire an action potential at any given point in time and how it will respond to similar inputs in the future. Two critical factors affect the integrative function of dendrites: the distribution of voltage-gated ion channels in the dendritic tree and the passive electrical properties, or 'electrotonic structure', upon which these active channels are superimposed. The authors review recent data from patch-clamp recordings that provide new estimates of the passive membrane properties of hippocampal neurons, and show, with examples, how these properties affect the shaping and attenuation of synaptic potentials as they propagate in the dendrites, as well as how they affect the measurement of current from synapses located in the dendrites. Voltage-gated channels might influence the measurement of 'passive' membrane properties and, reciprocally, passive membrane properties might affect the activation of voltage-gated channels in dendrites.
Animals↗
Mechanisms shaping glutamate-mediated excitatory postsynaptic currents in the CNS.
Excitatory postsynaptic currents in neurones of the central nervous system have a dual-component time course that results from the co-activation of AMPA/kainate-type and NMDA-type glutamate receptors. New approaches in electrophysiology and molecular biology have provided a better understanding of the factors that determine the kinetics of excitatory postsynaptic currents. Recent studies suggest that the time course of neurotransmitter concentration in the synaptic cleft, the gating properties of the native channels, and the glutamate receptor subunit composition all appear to be important factors.
Animals↗
Perforated patch-clamp analysis of the passive membrane properties of three classes of hippocampal neurons.
1. Perforated patch-clamp recordings were made from the three major classes of hippocampal neurons in conventional in vitro slices prepared from adult guinea pigs. This technique provided experimental estimates of passive membrane properties (input resistance, RN, and membrane time constant, tau m) determined in the absence of the leak conductance associated with microelectrode impalement or the washout of cytoplasmic constituents associated with conventional whole-cell recordings. 2. To facilitate comparison of our data with previous results and to determine the passive membrane properties under conditions as physiological as possible, recordings were made at the resting potential, in physiological saline, and without any added blockers of voltage-dependent conductances. 3. Membrane-potential responses to current steps were analyzed, and four criteria were used to identify voltage responses that were the least affected by activation of voltage-dependent conductances. tau m was estimated from the slowest component (tau 0) of multiexponential fits of responses deemed passive by these criteria. RN was estimated from the slope of the linear region in the hyperpolarizing direction of the voltage-current relation. 4. It was not possible to measure purely passive membrane properties that were completely independent of membrane potential in any of the three classes of hippocampal neurons. Changing the membrane potential by constant current injection resulted in changes in RN and tau 0; subthreshold depolarization produced an increase, and hyperpolarization a decrease, in both RN and tau 0 for all three classes of hippocampal neurons. 5. Each of the three classes of hippocampal neurons also displayed a depolarizing "sag" during larger hyperpolarizing voltage transients. To evaluate the effect of the conductances underlying this sag on passive membrane properties, 2-5 mM Cs+ was added to the physiological saline. Extracellular Cs+ effectively blocked the sag in all three classes of hippocampal neurons, but the effect of Cs+ on RN, tau 0, and the voltage dependence of these parameters was unique for each class of neurons. 6. CA1 pyramidal neurons had an RN of 104 +/- 10 (SE) M omega and tau 0 of 28 +/- 2 ms at a resting potential of -64 +/- 2 mV (n = 12). RN and tau 0 were larger at more depolarized potentials in these neurons, but the addition of Cs+ to the physiological saline reversed this voltage dependence. 7. CA3 pyramidal neurons had an RN of 135 +/- 8 M omega and tau 0 of 66 +/- 4 ms at a resting potential of -64 +/- 1 mV (n = 14).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Isolation from porcine intestinal extracts of a cholecystokinin-like peptide and a peptide with homology to cytochrome oxidase polypeptide VII and chymodenin.
A number of different forms of cholecystokinin (CCK) exist in the brain and intestine. Gel permeation and ion exchange chromatography and high performance liquid chromatography have been used to isolate a peptide from partially purified porcine intestinal extracts with N-terminal homology to porcine brain CCK-58. This peptide contracted both the guinea pig ileum longitudinal muscle and gallbladder muscle and these responses were inhibited by dibutyryl cyclic GMP or proglumide. The potency was approximately 1/100 of that of CCK-8. The reason for this low potency is unclear, but it is possible that a critical part of the biologically active region is modified or that it is a truncated form of CCK-58. A further peptide was isolated with a sequence homologous to cytochrome oxidase polypeptide VII and chymodenin.
Amino Acid Sequence↗