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Suzanne M. Moenter - One of the best experts on this subject based on the ideXlab platform.
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Chemogenetic Suppression of GnRH Neurons during Pubertal Development Can Alter Adult GnRH Neuron Firing Rate and Reproductive Parameters in Female Mice.
eNeuro, 2020Co-Authors: Eden A. Dulka, R. Anthony Defazio, Suzanne M. MoenterAbstract:Abstract Gonadotropin-releasing hormone (GnRH) neurons control anterior pituitary, and thereby gonadal, function. GnRH neurons are active before outward indicators of puberty appear. Prenatal androgen (PNA) exposure mimics reproductive dysfunction of the common fertility disorder polycystic ovary syndrome (PCOS) and reduces prepubertal GnRH neuron activity. Early neuron activity can play a critical role in establishing circuitry and adult function. We tested the hypothesis that changing prepubertal GnRH neuron activity programs adult GnRH neuron activity and reproduction independent of androgen exposure in female mice. Activating (3Dq) or inhibitory (4Di) designer receptors exclusively activated by designer drugs (DREADDs) were targeted to GnRH neurons using Cre-lox technology. In control studies, the DREADD ligand clozapine n-oxide (CNO) produced the expected changes in GnRH neuron activity in vitro and luteinizing hormone (LH) release in vivo. CNO was administered to control or PNA mice between two and three weeks of age, when GnRH neuron Firing Rate is reduced in PNA mice. In controls, reducing prepubertal GnRH neuron activity with 4Di increased adult GnRH neuron Firing Rate and days in diestrus but did not change puberty onset or GABA transmission to these cells. In contrast, activating GnRH neurons had no effect on reproductive parameters or Firing Rate and did not rescue reproductive phenotypes in PNA mice. These studies support the hypothesis that prepubertal neuronal activity sculpts elements of the adult reproductive neuroendocrine axis and cyclicity but indicate that other PNA-induced programming actions are required for full reproductive phenotypes and/or that compensatory mechanisms overcome activity-mediated changes to mitigate reproductive changes in adults.
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Ovarian Androgens Maintain High GnRH Neuron Firing Rate in Adult Prenatally-Androgenized Female Mice.
Endocrinology, 2019Co-Authors: Eden A. Dulka, Laura L. Burger, Suzanne M. MoenterAbstract:Changes in gonadotropin-releasing hormone (GnRH) release frequency from the brain help drive reproductive cycles. In polycystic ovary syndrome (PCOS), persistent high GnRH/luteinizing hormone (LH) frequency disrupts cycles and exacerbates hyperandrogenemia. Adult prenatally-androgenized (PNA) mice exhibit increased GnRH neuron Firing Rate, elevated ovarian androgens, and disrupted cycles, but before puberty, GnRH neuron activity is reduced in PNA mice compared with controls. We hypothesized that ovarian feedback mediates the age-dependent change in GnRH neuron Firing Rate in PNA vs control mice. Extracellular recordings of green fluorescent protein (GFP)-identified GnRH neurons were made 5 to 7 days after sham-surgery, ovariectomy (OVX), or, in adults, after OVX plus replacement of sub-male androgen levels with dihydrotestosterone implants (OVX + DHT). In 3-week-old mice, OVX did not affect GnRH neuron Firing Rate in either group. In adult controls, OVX increased GnRH neuron Firing Rate, which was further enhanced by DHT. In adult PNA mice, however, OVX decreased GnRH neuron Firing Rate, and DHT restored Firing Rate to sham-opeRated levels. In contrast to the differential effects of ovarian feedback on GnRH neuron Firing Rate, serum LH increased after OVX in both control and PNA mice and was not altered by DHT. Pituitary gene expression largely reflected changes expected with OVX, although in PNA but not control mice, DHT treatment increased Lhb expression. These results suggest prenatal androgen exposure programs marked changes in GnRH neuron regulation by homeostatic steroid feedback. PNA lowers GnRH neuron activity in low-steroid states (before puberty, OVX), and renders activity in adulthood dependent upon ongoing exposure to elevated ovarian androgens.
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endogenous activation of metabotropic glutamate receptors modulates gabaergic transmission to gonadotropin releasing hormone neurons and alters their Firing Rate a possible local feedback circuit
The Journal of Neuroscience, 2005Co-Authors: Zhiguo Chu, Suzanne M. MoenterAbstract:Gonadotropin-releasing hormone (GnRH) neurons are the primary central regulators of fertility, receiving input from GABAergic afferents via GABAA receptors. We tested whether metabotropic glutamate receptors (mGluRs) regulate GABA transmission to GnRH neurons and GnRH neuronal Firing pattern. Whole-cell recordings were performed under conditions isolating ionotropic GABA postsynaptic currents (PSCs) in brain slices. The broad-spectrum mGluR agonist 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) decreased the frequency of GABAA-mediated spontaneous PSCs in a reversible manner. Amplitude and kinetics were not altered, suggesting that afferent GABA neurons are the primary targets. TTX eliminated the effects of ACPD in most tested neurons. Group II [2-(2,3-dicarboxycyclopropyl) glycine] and III (l-AP-4) mGluR agonists mediated this response; a group I agonist (3,5-dihydroxyphenylglycine) was not effective. The broad-spectrum antagonist α-methyl-4-carboxyphenylglycine (MCPG) and/or (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG) (group III antagonist) enhanced spontaneous PSC frequency, particularly when initial frequency was low, suggesting that endogenous activation of mGluRs regulates GABA transmission to GnRH neurons. Extracellular recordings were used to evaluate GnRH neuron Firing Rate within the network. ACPD reduced Firing Rate, and MCPG plus CPPG had an opposite effect, indicating that mGluRs help control excitability of the GnRH network. GnRH neurons express vesicular glutamate transporters, suggesting they may corelease this transmitter. Simulation of Firing activity in a GnRH neuron decreased PSC frequency in that cell, an effect blocked by antagonism of mGluRs but not GnRH receptors. These results demonstRate an inhibition of GABAergic inputs to GnRH neurons by mGluRs via a presynaptic mechanism. Through this mechanism, local glutamate milieu, possibly contributed by GnRH neurons themselves, plays an important role in modulating GnRH release and the central regulation of fertility.
Adam Hockley - One of the best experts on this subject based on the ideXlab platform.
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nitric oxide regulates the Firing Rate of neuronal subtypes in the guinea pig ventral cochlear nucleus
European Journal of Neuroscience, 2020Co-Authors: Adam Hockley, Joel I Berger, Alan R Palmer, Paul A Smith, Mark N WallaceAbstract:The gaseous free radical, nitric oxide (NO) acts as a ubiquitous neuromodulator, contributing to synaptic plasticity in a complex way that can involve either long term potentiation or depression. It is produced by neuronal nitric oxide synthase (nNOS) which is presynaptically expressed and also located postsynaptically in the membrane and cytoplasm of a subpopulation of each major neuronal type in the ventral cochlear nucleus (VCN). We have used iontophoresis in vivo to study the effect of the NOS inhibitor L-NAME (L-NG-Nitroarginine methyl ester) and the NO donors SIN-1 (3-Morpholinosydnonimine hydrochloride) and SNOG (S-Nitrosoglutathione) on VCN units under urethane anaesthesia. Collectively, both donors produced increases and decreases in driven and spontaneous Firing Rates of some neurones. Inhibition of endogenous NO production with L-NAME evoked a consistent increase in driven Firing Rates in 18% of units without much effect on spontaneous Rate. This reduction of gain produced by endogenous NO was mirrored when studying the effect of L-NAME on NMDA(N-Methyl-D-aspartic acid)-evoked excitation, with 30% of units showing enhanced NMDA-evoked excitation during L-NAME application (reduced NO levels). Approximately 25% of neurones contain nNOS and the NO produced can modulate the Firing Rate of the main principal cells: medium stellates (choppers), large stellates (onset responses) and bushy cells (primary-like responses). The main endogenous role of NO seems to be to partly suppress driven Firing Rates associated with NMDA channel activity but there is scope for it to increase neural gain if there were a pathological increase in its production following hearing loss.
Nicolas Brunel - One of the best experts on this subject based on the ideXlab platform.
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analytical approximations of the Firing Rate of an adaptive exponential integRate and fire neuron in the presence of synaptic noise
Frontiers in Computational Neuroscience, 2014Co-Authors: Loreen Hertag, Daniel Durstewitz, Nicolas BrunelAbstract:Computational models offer a unique tool for understanding the network-dynamical mechanisms which mediate between physiological and biophysical properties, and behavioral function. A traditional challenge in computational neuroscience is, however, that simple neuronal models which can be studied analytically fail to reproduce the diversity of electrophysiological behaviors seen in real neurons, while detailed neuronal models which do reproduce such diversity are intractable analytically and computationally expensive. A number of intermediate models have been proposed whose aim is to capture the diversity of Firing behaviors and spike times of real neurons while entailing a mathematical description as simple as possible. One such model is the exponential integRate-and-fire neuron with spike Rate adaptation (aEIF) which consists of two differential equations for the membrane potential (V) and an adaptation current (w). Despite its simplicity, it can reproduce a wide variety of physiologically observed spiking patterns, can be fit to physiological recordings quantitatively, and, once done so, is able to predict spike times on traces not used for model fitting. Here we compute the steady-state Firing Rate of aEIF in the presence of Gaussian synaptic noise, using two approaches. The first approach is based on the 2-dimensional Fokker-Planck equation that describes the (V,w)-probability distribution, which is solved using an expansion in the ratio between the time constants of the two variables. The second is based on the Firing Rate of the EIF model, which is averaged over the distribution of the $w$ variable. These analytically derived closed-form expressions were tested on simulations from a large variety of model cells quantitatively fitted to in vitro electrophysiological recordings from pyramidal cells and interneurons. Theoretical predictions closely agreed with the Firing Rate of the simulated cells fed with in-vivo-like synaptic noise.
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dynamics of the instantaneous Firing Rate in response to changes in input statistics
Journal of Computational Neuroscience, 2005Co-Authors: Nicolas Fourcaudtrocme, Nicolas BrunelAbstract:We review and extend recent results on the instantaneous Firing Rate dynamics of simplified models of spiking neurons in response to noisy current inputs. It has been shown recently that the response of the instantaneous Firing Rate to small amplitude oscillations in the mean inputs depends in the large frequency limit f on the spike initiation dynamics. A particular simplified model, the exponential integRate-and-fire (EIF) model, has a response that decays as 1/f in the large frequency limit and describes very well the response of conductance-based models with a Hodgkin-Huxley type fast sodium current. Here, we show that the response of the EIF instantaneous Firing Rate also decays as 1/f in the case of an oscillation in the variance of the inputs for both white and colored noise. We then compute the initial transient response of the Firing Rate of the EIF model to a step change in its mean inputs and/or in the variance of its inputs. We show that in both cases the response speed is proportional to the neuron stationary Firing Rate and inversely proportional to a ‘spike slope factor’ Δ T that controls the sharpness of spike initiation: as 1/Δ T for a step change in mean inputs, and as 1/Δ T 2 for a step change in the variance in the inputs.
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Firing Rate of the noisy quadratic integRate and fire neuron
Neural Computation, 2003Co-Authors: Nicolas Brunel, P E LathamAbstract:We calculate the Firing Rate of the quadratic integRate-and-fire neuron in response to a colored noise input current. Such an input current is a good approximation to the noise due to the random bombardment of spikes, with the correlation time of the noise corresponding to the decay time of the synapses. The key parameter that determines the Firing Rate is the ratio of the correlation time of the colored noise, τs, to the neuronal time constant, τm. We calculate the Firing Rate exactly in two limits: when the ratio, τs/τm, goes to zero (white noise) and when it goes to infinity. The correction to the short correlation time limit is O(τs/τm), which is qualitatively different from that of the leaky integRate-and-fire neuron, where the correction is O(√τs/τm). The difference is due to the different boundary conditions of the probability density function of the membrane potential of the neuron at Firing threshold. The correction to the long correlation time limit is O(τm/τs). By combining the short and long correlation time limits, we derive an expression that provides a good approximation to the Firing Rate over the whole range of τs/τm in the suprathreshold regime-- that is, in a regime in which the average current is sufficient to make the cell fire. In the subthreshold regime, the expression breaks down somewhat when τs becomes large compared to τm.
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Firing Rate resonance in a generalized integRate and fire neuron with subthreshold resonance
Physical Review E, 2003Co-Authors: Nicolas Brunel, Vincent Hakim, Magnus J E RichardsonAbstract:Neurons that exhibit a peak at finite frequency in their membrane potential response to oscillatory inputs are widespread in the nervous system. However, the influence of this subthreshold resonance on spiking properties has not yet been thoroughly analyzed. To this end, generalized integRate-and-fire models are introduced that reproduce at the linear level the subthreshold behavior of any given conductance-based model. A detailed analysis is presented of the simplest resonant model of this kind that has two variables: the membrane potential and a supplementary voltage-gated resonant variable. The Firing-Rate modulation created by a noisy weak oscillatory drive, mimicking an in vivo environment, is computed numerically and analytically when the dynamics of the resonant variable is slow compared to that of the membrane potential. The results show that the Firing-Rate modulation is shaped by the subthreshold resonance. For weak noise, the Firing-Rate modulation has a minimum near the preferred subthreshold frequency. For higher noise, such as that prevailing in vivo, the Firing-Rate modulation peaks near the preferred subthreshold frequency.
Mark N Wallace - One of the best experts on this subject based on the ideXlab platform.
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nitric oxide regulates the Firing Rate of neuronal subtypes in the guinea pig ventral cochlear nucleus
European Journal of Neuroscience, 2020Co-Authors: Adam Hockley, Joel I Berger, Alan R Palmer, Paul A Smith, Mark N WallaceAbstract:The gaseous free radical, nitric oxide (NO) acts as a ubiquitous neuromodulator, contributing to synaptic plasticity in a complex way that can involve either long term potentiation or depression. It is produced by neuronal nitric oxide synthase (nNOS) which is presynaptically expressed and also located postsynaptically in the membrane and cytoplasm of a subpopulation of each major neuronal type in the ventral cochlear nucleus (VCN). We have used iontophoresis in vivo to study the effect of the NOS inhibitor L-NAME (L-NG-Nitroarginine methyl ester) and the NO donors SIN-1 (3-Morpholinosydnonimine hydrochloride) and SNOG (S-Nitrosoglutathione) on VCN units under urethane anaesthesia. Collectively, both donors produced increases and decreases in driven and spontaneous Firing Rates of some neurones. Inhibition of endogenous NO production with L-NAME evoked a consistent increase in driven Firing Rates in 18% of units without much effect on spontaneous Rate. This reduction of gain produced by endogenous NO was mirrored when studying the effect of L-NAME on NMDA(N-Methyl-D-aspartic acid)-evoked excitation, with 30% of units showing enhanced NMDA-evoked excitation during L-NAME application (reduced NO levels). Approximately 25% of neurones contain nNOS and the NO produced can modulate the Firing Rate of the main principal cells: medium stellates (choppers), large stellates (onset responses) and bushy cells (primary-like responses). The main endogenous role of NO seems to be to partly suppress driven Firing Rates associated with NMDA channel activity but there is scope for it to increase neural gain if there were a pathological increase in its production following hearing loss.
Matteo Carandini - One of the best experts on this subject based on the ideXlab platform.
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membrane potential and Firing Rate in cat primary visual cortex
The Journal of Neuroscience, 2000Co-Authors: Matteo Carandini, David FersterAbstract:We have investigated the relationship between membrane potential and Firing Rate in cat visual cortex and found that the spike threshold contributes substantially to the sharpness of orientation tuning. The half-width at half-height of the tuning of the spike responses was 23 ± 8°, compared with 38 ± 15° for the membrane potential responses. Direction selectivity was also greater in spike responses (direction index, 0.61 ± 0.35) than in membrane potential responses (0.28 ± 0.21). Threshold also increased the distinction between simple and complex cells, which is commonly based on the linearity of the spike responses to drifting sinusoidal gratings. In many simple cells, such stimuli evoked substantial elevations in the mean potential, which are nonlinear. Being subthreshold, these elevations would be hard to detect in the Firing Rate responses. Moreover, just as simple cells displayed various degrees of nonlinearity, complex cells displayed various degrees of linearity. We fitted the Firing Rates with a classic rectification model in which Firing Rate is zero at potentials below a threshold and grows linearly with the potential above threshold. When the model was applied to a low-pass-filtered version of the membrane potential (with spikes removed), the estimated values of threshold (−54.4 ± 1.4 mV) and linear gain (7.2 ± 0.6 spikes · sec−1 · mV−1) were similar across the population. The predicted Firing Rates matched the observed Firing Rates well and accounted for the sharpening of orientation tuning of the spike responses relative to that of the membrane potential. As it was for stimulus orientation, threshold was also independent of stimulus contrast. The rectification model accounted for the dependence of spike responses on contrast and, because of a stimulus-induced tonic hyperpolarization, for the response adaptation induced by prolonged stimulation. Because gain and threshold are unaffected by visual stimulation and by adaptation, we suggest that they are constant under all conditions.