scholarly journals Extraction of Synaptic Input Properties in Vivo

2017 ◽  
Vol 29 (7) ◽  
pp. 1745-1768 ◽  
Author(s):  
Paolo Puggioni ◽  
Marta Jelitai ◽  
Ian Duguid ◽  
Mark C.W. van Rossum
Keyword(s):  
Voltage Clamp ◽  
Synaptic Input ◽  
Event Rate ◽  
Synaptic Integration ◽  
Neural Function ◽  
State Change ◽  
Input Rate ◽  
Time Constants ◽  
Synaptic Inputs

Knowledge of synaptic input is crucial for understanding synaptic integration and ultimately neural function. However, in vivo, the rates at which synaptic inputs arrive are high, so that it is typically impossible to detect single events. We show here that it is nevertheless possible to extract the properties of the events and, in particular, to extract the event rate, the synaptic time constants, and the properties of the event size distribution from in vivo voltage-clamp recordings. Applied to cerebellar interneurons, our method reveals that the synaptic input rate increases from 600 Hz during rest to 1000 Hz during locomotion, while the amplitude and shape of the synaptic events are unaffected by this state change. This method thus complements existing methods to measure neural function in vivo.

scholarly journals Active membrane conductances and morphology of a collision detection neuron broaden its impedance profile and improve membrane synchrony

2018 ◽  
Author(s):  
Richard Dewell ◽  
Fabrizio Gabbiani
Keyword(s):  
Synaptic Input ◽  
Collision Detection ◽  
Dendritic Morphology ◽  
Synaptic Integration ◽  
Neuronal Membrane ◽  
Hcn Channels ◽  
Movement Detector ◽  
Membrane Impedance ◽  
Wide Range

Brains processes information through the coordinated efforts of billions of individual neurons, each encoding a small part of the overall information stream. Central to this is how neurons integrate and transform complex patterns of synaptic inputs. The neuronal membrane impedance sets the gain and timing for synaptic integration, determining a neuron's ability to discriminate between synaptic input patterns. Using single and dual dendritic recordings in vivo, pharmacology, and computational modeling, we characterized the membrane impedance of a collision detection neuron in the grasshopper, Schistocerca americana. We examined how the cellular properties of the lobula giant movement detector (LGMD) neuron are tuned to enable the discrimination of synaptic input patterns key to its role in collision detection. We found that two common active conductances gH and gM, mediated respectively by hyperpolarization-activated cyclic nucleotide gated (HCN) channels and by muscarine sensitive M-type K+ channels, promote broadband integration with high temporal precision over the LGMD's natural range of membrane potentials and synaptic input frequencies. Additionally, we found that the LGMD's branching morphology increased the gain and decreased delays associated with the mapping of synaptic input currents to membrane potential. We investigated whether other branching dendritic morphologies fulfill a similar function and found this to be true for a wide range of morphologies, including those of neocortical pyramidal neurons and cerebellar Purkinje cells. These findings further our understanding of the integration properties of individual neurons by showing the unexpected role played by two widespread active conductances and by dendritic morphology in shaping synaptic integration.

scholarly journals Different dendritic domains of the GnRH neuron underlie the pulse and surge modes of GnRH secretion in female mice

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Li Wang ◽  
Wenya Guo ◽  
Xi Shen ◽  
Shel Yeo ◽  
Hui Long ◽  
...  
Keyword(s):  
Synaptic Integration ◽  
Secretory Process ◽  
Gnrh Neuron ◽  
Lh Surge ◽  
Synaptic Inputs ◽  
Gnrh Secretion ◽  
Pulsatile Gnrh ◽  
Lh Pulsatility ◽  
Neuron Soma

The gonadotropin-releasing hormone (GnRH) neurons exhibit pulse and surge modes of activity to control fertility. They also exhibit an unusual bipolar morphology comprised of a classical soma-proximal dendritic zone and an elongated secretory process that can operate as both a dendrite and an axon, termed a ‘dendron’. We show using expansion microscopy that the highest density of synaptic inputs to a GnRH neuron exists at its distal dendron. In vivo, selective chemogenetic inhibition of the GnRH neuron distal dendron abolishes the luteinizing hormone (LH) surge and markedly dampens LH pulses. In contrast, inhibitory chemogenetic and optogenetic strategies targeting the GnRH neuron soma-proximal dendritic zone abolish the LH surge but have no effect upon LH pulsatility. These observations indicate that electrical activity at the soma-proximal dendrites of the GnRH neuron is only essential for the LH surge while the distal dendron represents an autonomous zone where synaptic integration drives pulsatile GnRH secretion.

scholarly journals Amplification and Linear Summation of Synaptic Effects on Motoneuron Firing Rate

2001 ◽  
Vol 85 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Jonathan F. Prather ◽  
Randall K. Powers ◽  
Timothy C. Cope
Keyword(s):  
Firing Rate ◽  
Synaptic Input ◽  
Synaptic Integration ◽  
Medial Gastrocnemius ◽  
Resting Potential ◽  
Repetitive Firing ◽  
Linear Summation ◽  
Decerebrate Cat ◽  
Inward Current ◽  
Synaptic Inputs

The aim of this study was to measure the effects of synaptic input on motoneuron firing rate in an unanesthetized cat preparation, where activation of voltage-sensitive dendritic conductances may influence synaptic integration and repetitive firing. In anesthetized cats, the change in firing rate produced by a steady synaptic input is approximately equal to the product of the effective synaptic current measured at the resting potential ( I N) and the slope of the linear relation between somatically injected current and motoneuron discharge rate ( f-I slope). However, previous studies in the unanesthetized decerebrate cat indicate that firing rate modulation may be strongly influenced by voltage-dependent dendritic conductances. To quantify the effects of these conductances on motoneuron firing behavior, we injected suprathreshold current steps into medial gastrocnemius motoneurons of decerebrate cats and measured the changes in firing rate produced by superimposed excitatory synaptic input. In the same cells, we measured I N and the f-I slope to determine the predicted change in firing rate (Δ F = I N * f-I slope). In contrast to previous results in anesthetized cats, synaptically induced changes in motoneuron firing rate were greater-than-predicted. This enhanced effect indicates that additional inward current was present during repetitive firing. This additional inward current amplified the effective synaptic currents produced by two different excitatory sources, group Ia muscle spindle afferents and caudal cutaneous sural nerve afferents. There was a trend toward more prevalent amplification of the Ia input (14/16 cells) than the sural input (11/16 cells). However, in those cells where both inputs were amplified (10/16 cells), amplification was similar in magnitude for each source. When these two synaptic inputs were simultaneously activated, their combined effect was generally very close to the linear sum of their amplified individual effects. Linear summation is also observed in medial gastrocnemius motoneurons of anesthetized cats, where amplification is not present. This similarity suggests that amplification does not disturb the processes of synaptic integration. Linear summation of amplified input was evident for the two segmental inputs studied here. If these phenomena also hold for other synaptic sources, then the presence of active dendritic conductances underlying amplification might enable motoneurons to integrate multiple synaptic inputs and drive motoneuron firing rates throughout the entire physiological range in a relatively simple fashion.

Computer simulations of the effects of different synaptic input systems on motor unit recruitment

1993 ◽  
Vol 70 (5) ◽  
pp. 1827-1840 ◽  
Author(s):  
C. J. Heckman ◽  
M. D. Binder
Keyword(s):  
Motor Unit ◽  
Computer Simulations ◽  
Synaptic Input ◽  
Reciprocal Inhibition ◽  
Excitatory Input ◽  
Medial Gastrocnemius ◽  
Synaptic Inputs ◽  
Monte Carlo Techniques ◽  
Recruitment Order ◽  
Random Variance

1. The effects of four different synaptic input systems on the recruitment order within a mammalian motoneuron pool were investigated using computer simulations. The synaptic inputs and motor unit properties in the model were based as closely as possible on the available experimental data for the cat medial gastrocnemius pool and muscle. Monte Carlo techniques were employed to add random variance to the motor unit thresholds and forces and to sample the resulting recruitment orders. 2. The effects of the synaptic inputs on recruitment order depended on how they modified the range of recruitment thresholds established by differences in the intrinsic current thresholds of the motoneurons. Application of a uniform synaptic input to the pool (i.e., distributed equally to all motoneurons) resulted in a recruitment sequence that was quite stable even with the addition of large amounts of random variance. With 50% added random variance, the recruitment reversals did not exceed 8%. 3. The simulated monosynaptic input from homonymous Ia afferent fibers generated a twofold expansion of the range of recruitment thresholds beyond that attributed to the differences in the intrinsic current thresholds. The Ia input generated a small reduction in the number of recruitment reversals due to random variance (6% reversals at 50% random variance). The simulated monosynaptic vestibulospinal input generated a twofold compression of the range of recruitment thresholds that exerted a modest increase in the number of recruitment reversals (12% reversals at 50% random variance). 4. In comparison with the modest effects of the two monosynaptic inputs, the simulated oligosynpatic rubrospinal excitatory input exerted a nine-fold compression in the recruitment threshold range that resulted in a recruitment sequence that was highly sensitive to random variance. With 50% added random variance, the sequence became nearly random (40% reversals). 5. Reciprocal Ia inhibition was simulated by a uniform distribution within the pool, but its effects on recruitment order were highly dependent on the distribution of the excitatory input. Reciprocal inhibition exerted only minor effects on recruitment order when combined with the Ia or vestibulospinal inputs. However, when the excitatory drive was supplied by the rubrospinal input, even small amounts of reciprocal inhibition were sufficient to completely reverse the normal recruitment sequence. 6. The simulated monosynaptic Ia input was highly effective in compensating for the disruptive effects of rubrospinal excitation on recruitment order. Even a small Ia bias combined with the rubrospinal excitation was sufficient to halve the effects of random variance and to restore the normal recruitment sequence in the presence of rather large amounts of reciprocal inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of anomalous rectifier activation on afterhyperpolarizations of neurons from cat sensorimotor cortex in vitro

1988 ◽  
Vol 59 (2) ◽  
pp. 468-481 ◽  
Author(s):  
P. C. Schwindt ◽  
W. J. Spain ◽  
W. E. Crill
Keyword(s):  
Membrane Potential ◽  
Voltage Clamp ◽  
Sensorimotor Cortex ◽  
Model Parameters ◽  
Fast Decay ◽  
Time Constants ◽  
Anomalous Rectifier ◽  
Betz Cells ◽  
K Currents

1. Large neurons from layer V of cat sensorimotor cortex (Betz cells) were studied to determine the influence of the anomalous rectifier current (IAR) on slow afterhyperpolarizations (AHPs). The neurons were examined using intracellular recording and single-microelectrode voltage clamp in an in vitro brain slice preparation. 2. A faster medium-duration AHP (mAHP) and slower AHP (sAHP) followed repetitive firing (22, 23). The amplitude of the mAHP often increased or remained constant during membrane potential hyperpolarization. The membrane potential trajectory resulting solely from IAR activation was similar to the mAHP. 3. Postrepetitive firing voltage clamp was used to measure directly slowly decaying K+ currents (IK) and IAR at different membrane potentials. IK exhibited both a fast and slow decay. The time constants of the fast decay of IK and IAR activation were similar. IAR increased with hyperpolarization or raised extracellular K+ concentration [( K+]o), whereas both the fast and slow components of IK reversed or nulled near -100 mV and behaved as pure K+ currents in response to raised [K+]o. 4. To determine the precise contribution of IK and IAR to the AHP waveform, theoretical AHPs were computed using a quantitative model based on voltage-clamp measurements. The calculated AHPs were qualitatively similar to measured AHPs. The amplitude of the mAHP showed little change with hyperpolarization because of the increasing dominance of IAR at more negative membrane potentials. The sAHP was little affected by IAR activation. 5. Several model parameters subject to biological variation among Betz cells were varied in the calculations to determine their importance in the AHP waveform. With IK parameters held constant, the amplitude and time course of the mAHP depended on resting potential, membrane time constant, the kinetics of the anomalous rectifier conductance (GAR), and the maximum value of GAR. IAR activation could result in a biphasic AHP even when the fast decay of IK was omitted from the calculations. 6. A wider variation of model parameters revealed behavior that may be relevant to other neurons. Certain values of membrane or IAR activation time constants resulted in a monophasic AHP even when the fast decay of IK was present. The decay of a biphasic AHP could reflect either the onset of IAR or the fast decay of IK, depending on the relative value of their time constants. Procedures are outlined to discriminate between these possibilities using current clamp methods.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Differences in spike generation instead of synaptic inputs determine the feature selectivity of two retinal cell types.

2021 ◽  
Author(s):  
Sophia Wienbar ◽  
Gregory Schwartz
Keyword(s):  
Synaptic Input ◽  
Ganglion Cells ◽  
Intrinsic Property ◽  
Retinal Cell ◽  
Projection Neurons ◽  
Functional Difference ◽  
Intrinsic Properties ◽  
Spike Generation ◽  
Synaptic Inputs ◽  
Feature Selectivity

The output of spiking neurons depends both on their synaptic inputs and on their intrinsic properties. Retinal ganglion cells (RGCs), the spiking projection neurons of the retina, comprise over 40 different types in mice and other mammals, each tuned to different features of visual scenes. The circuits providing synaptic input to different RGC types to drive feature selectivity have been studied extensively, but there has been substantially less research aimed at understanding how the intrinsic properties of RGCs differ and how those differences impact feature selectivity. Here, we introduce an RGC type in the mouse, the Bursty Suppressed-by-Contrast (bSbC) RGC, whose contrast selectivity is shaped by its intrinsic properties. Surprisingly, when we compare the bSbC RGC to the OFF sustained alpha (OFFsA) RGC that receives similar synaptic input, we find that the two RGC types exhibit starkly different responses to an identical stimulus. We identified spike generation as the key intrinsic property behind this functional difference; the bSbC RGC undergoes depolarization block in conditions where the OFFsA RGC maintains a high spike rate. Pharmacological experiments, imaging, and compartment modeling demonstrate that these differences in spike generation are the result of differences in voltage-gated sodium channel conductances. Our results demonstrate that differences in intrinsic properties allow these two RGC types to detect and relay distinct features of an identical visual stimulus to the brain.

scholarly journals Anatomic and Biochemical Correlates of the Dopamine Transporter Ligand 11C-PE2I in Normal and Parkinsonian Primates: Comparison with 6-[18F]Fluoro-L-Dopa

2001 ◽  
Vol 21 (7) ◽  
pp. 782-792 ◽  
Author(s):  
Thomas Poyot ◽  
Françoise Condé ◽  
Marie-Claude Grégoire ◽  
Vincent Frouin ◽  
Christine Coulon ◽  
...  
Keyword(s):  
Gold Standard ◽  
Dopaminergic Neurons ◽  
Emission Tomography ◽  
Attractive Alternative ◽  
Input Rate ◽  
Nigrostriatal Pathway ◽  
Positron Emission ◽  
Neuroprotective Strategies

Positron emission tomography (PET) coupled to 6-[18F]Fluoro-L-Dopa (18F-Dopa) remains the gold standard for assessing dysfunctionality concerning the dopaminergic nigrostriatal pathway in Parkinson's disease and related disorders. The use of ligands of the dopamine transporters (DAT) is an attractive alternative target; consequently, the current aim was to validate one of them, 11C-PE2I, using a multiinjection modeling approach allowing accurate quantitation of DAT densities in the striatum. Experiments were performed in three controls, three MPTP-treated (parkinsonian) baboons, and one reserpine-treated baboon. 11C-PE2I B′max values obtained with this approach were compared with 18F-Dopa input rate constant values (Ki), in vitro Bmax binding of 125I-PE2I, and the number of dopaminergic neurons in the substantia nigra estimated postmortem by stereology. In the caudate nucleus and putamen, control values for 11C-PE2I B'max were 673 and 658 pmol/mL, respectively, whereas it was strongly reduced in the MPTP-treated (B′max = 26 and 36 pmol/mL) and reserpine-treated animals (B′max = 338 and 483 pmol/mL). In vivo11C-PE2I B′max values correlated with 18F-Dopa Ki values and in vitro125I-PE2I Bmax values in the striatum and with the number of nigral dopaminergic neurons. Altogether, these data support the use of 11C-PE2I for monitoring striatal dopaminergic disorders and the effect of potential neuroprotective strategies.

scholarly journals Dendrite-Specific Amplification of Weak Synaptic Input during Network Activity In Vivo

Cell Reports ◽  
2018 ◽  
Vol 24 (13) ◽  
pp. 3455-3465.e5 ◽  
Author(s):  
Leiron Ferrarese ◽  
Jean-Sébastien Jouhanneau ◽  
Michiel W.H. Remme ◽  
Jens Kremkow ◽  
Gergely Katona ◽  
...  
Keyword(s):  
Synaptic Input ◽  
Network Activity ◽  
Specific Amplification

Local mechanisms of phase-dependent postsynaptic modifications of NMDA-induced oscillations in the abducens motoneurons: a simulation study

1996 ◽  
Vol 76 (2) ◽  
pp. 1015-1024 ◽  
Author(s):  
I. L. Kopysova ◽  
S. M. Korogod ◽  
J. Durand ◽  
S. Tyc-Dumont
Keyword(s):  
Synaptic Input ◽  
Pattern Generation ◽  
Ion Concentration ◽  
Extracellular Potassium ◽  
Pump System ◽  
Voltage Gated ◽  
Ion Concentrations ◽  
Concentration Changes ◽  
Transmembrane Currents

1. In vivo experiments have shown that extracellular microelectrophoretic application of N-methyl-D-aspartate (NMDA) induced oscillatory plateau potentials with bursts of action potentials in rat abducens motoneurons. The period of these slow NMDA oscillations could be altered by single trigeminal non-NMDA excitatory input delivered at low frequency during the NMDA oscillations. 2. A resetting of the oscillations was observed depending on the phase of slow oscillatory cycle during which the trigeminal excitation occurred. 3. We investigated local mechanisms responsible for the phase-dependent modifications of NMDA oscillations, including contributions of voltage and concentration transients, in the mathematical model of the isopotential membrane compartment equipped with voltage-gated Na+, K+, and Ca2+ channels, with Ca2+-dependent K+ channels, and with ligand-gated NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels. The faithful model was constructed with the use of models described earlier, which were modified by increasing time constants of kinetic variables of all voltage-gated conductances and by including coupled dynamics of voltages and ion concentrations. The changes in ion concentrations were produced near the membrane by transmembrane currents and removal mechanisms (pumps, diffusion). 4. This work focuses on local arrangement of voltage- and ligand-gated conductances and on local ion concentration changes in two separate pools: the postsynaptic pool of AMPA receptors and the extrasynaptic pool. In terms of the electrotonic and diffusional length constants, these pools were electrotonically close but diffusionally remote. 5. It was found that the effect of resetting can be produced by a local interaction between plateau and spike-generating conductances and glutamate receptors. 6. In vivo phase-dependent interactions between NMDA oscillations and AMPA synaptic input were reproduced by the local model only when changes in intracellular sodium and extracellular potassium concentrations were taken into account and the mechanisms of ion removal from postsynaptic pools had slower kinetics than the fast pump system operating in the extracellular pool. 7. Postsynaptic changes in ion concentrations of Na+ and K+ in intra- and extracellular layers near the membrane shift of Nernst equilibrium potentials for these ions depending on the phase of activation of synaptic input. Thus Na+ and k+ components of all transmembrane currents involved in the pattern generation are differently affected by synaptic action during the oscillations. We conclude that slow postsynaptic changes in ion concentrations near the membrane play a key role in the resetting of the NMDA oscillations.

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