Restoration of descending inputs fails to rescue activity following deafferentation of a motor network

2012 ◽  
Vol 108 (3) ◽  
pp. 871-881 ◽  
Author(s):  
Jebun Nahar ◽  
Kawasi M. Lett ◽  
David J. Schulz
Keyword(s):  
Time Course ◽  
Critical Role ◽  
Stomatogastric Ganglion ◽  
Homeostatic Plasticity ◽  
Projection Neurons ◽  
Cancer Borealis ◽  
Compensatory Response ◽  
Pyloric Network ◽  
Motor Network ◽  
Network Output

Motor networks such as the pyloric network of the stomatogastric ganglion often require descending neuromodulatory inputs to initiate, regulate, and modulate their activity and their synaptic connectivity to manifest physiologically appropriate output. Prolonged removal of these descending inputs often results in a compensatory response that alters the inputs themselves, their targets, or both. Using the pyloric network of the crab, Cancer borealis, we investigated whether isolation of motor networks would result in alterations that change the responses of these networks to restored modulatory input. We used a reversible block with isotonic sucrose to transiently alter descending inputs into the pyloric network of the crab stomatogastric ganglion. Using this method, we found that blocking neuromodulatory inputs caused a reduced ability for subsequently restored modulatory projections to appropriately generate network output. Our results suggest that this could be due to changes in activity of descending projection neurons as well as changes in sensitivity to neuromodulators of the target neurons that develop over the time course of the blockade. These findings suggest that although homeostatic plasticity may play a critical role in recovery of functional output in a deafferented motor network, the results of these compensatory changes may alter the network such that restored inputs no longer function appropriately.

scholarly journals Differential Modulation of Synaptic Strength and Timing Regulate Synaptic Efficacy in a Motor Network

2011 ◽  
Vol 105 (1) ◽  
pp. 293-304 ◽  
Author(s):  
Bruce R. Johnson ◽  
Jessica M. Brown ◽  
Mark D. Kvarta ◽  
Jay Y. J. Lu ◽  
Lauren R. Schneider ◽  
...  
Keyword(s):  
Synaptic Input ◽  
Synaptic Strength ◽  
Neuronal Firing ◽  
Cycle Period ◽  
Cycle Frequency ◽  
Pyloric Network ◽  
Motor Network ◽  
Pyloric Dilator ◽  
Network Output ◽  
Firing Properties

Neuromodulators modify network output by altering neuronal firing properties and synaptic strength at multiple sites; however, the functional importance of each site is often unclear. We determined the importance of monoamine modulation of a single synapse for regulation of network cycle frequency in the oscillatory pyloric network of the lobster. The pacemaker kernel of the pyloric network receives only one chemical synaptic feedback, an inhibitory synapse from the lateral pyloric (LP) neuron to the pyloric dilator (PD) neurons, which can limit cycle frequency. We measured the effects of dopamine (DA), octopamine (Oct), and serotonin (5HT) on the strength of the LP→PD synapse and the ability of the modified synapse to regulate pyloric cycle frequency. DA and Oct strengthened, whereas 5HT weakened, LP→PD inhibition. Surprisingly, the DA-strengthened LP→PD synapse lost its ability to slow the pyloric oscillations, whereas the 5HT-weakened LP→PD synapse gained a greater influence on the oscillations. These results are explained by monoamine modulation of factors that determine the firing phase of the LP neuron in each cycle. DA acts via multiple mechanisms to phase-advance the LP neuron into the pacemaker's refractory period, where the strengthened synapse has little effect. In contrast, 5HT phase-delays LP activity into a region of greater pacemaker sensitivity to LP synaptic input. Only Oct enhanced LP regulation of cycle period simply by enhancing LP→PD synaptic strength. These results show that modulation of the strength and timing of a synaptic input can differentially affect the synapse's efficacy in the network.

scholarly journals Episodic Bouts of Activity Accompany Recovery of Rhythmic Output By a Neuromodulator- and Activity-Deprived Adult Neural Network

2003 ◽  
Vol 90 (4) ◽  
pp. 2720-2730 ◽  
Author(s):  
Jason A. Luther ◽  
Alice A. Robie ◽  
John Yarotsky ◽  
Christopher Reina ◽  
Eve Marder ◽  
...  
Keyword(s):  
Neural Network ◽  
Neuronal Network ◽  
Recovery Process ◽  
Stomatogastric Ganglion ◽  
Cancer Borealis ◽  
Pyloric Network ◽  
Underlying Mechanisms ◽  
Over Time ◽  
Phase Relationships ◽  
Pyloric Rhythm

The pyloric rhythm of the stomatogastric ganglion of the crab, Cancer borealis, slows or stops when descending modulatory inputs are acutely removed. However, the rhythm spontaneously resumes after one or more days in the absence of neuromodulatory input. We recorded continuously for days to characterize quantitatively this recovery process. Activity bouts lasting 40–900 s began several hours after removal of neuromodulatory input and were followed by stable rhythm recovery after 1–4 days. Bout duration was not related to the intervals (0.3–800 min) between bouts. During an individual bout, the frequency rapidly increased and then decreased more slowly. Photoablation of back-filled neuromodulatory terminals in the stomatogastric ganglion (STG) neuropil had no effect on activity bouts or recovery, suggesting that these processes are intrinsic to the STG neuronal network. After removal of neuromodulatory input, the phase relationships of the components of the triphasic pyloric rhythm were altered, and then over time the phase relationships moved toward their control values. Although at low pyloric rhythm frequency the phase relationships among pyloric network neurons depended on frequency, the changes in frequency during recovery did not completely account for the change in phase seen after rhythm recovery. We suggest that activity bouts represent underlying mechanisms controlling the restructuring of the pyloric network to allow resumption of an appropriate output after removal of neuromodulatory input.

GABA and responses to GABA in the stomatogastric ganglion of the crab Cancer borealis

2000 ◽  
Vol 203 (14) ◽  
pp. 2075-2092 ◽  
Author(s):  
A.M. Swensen ◽  
J. Golowasch ◽  
A.E. Christie ◽  
M.J. Coleman ◽  
M.P. Nusbaum ◽  
...  
Keyword(s):  
Nervous System ◽  
Gaba Receptors ◽  
Reversal Potential ◽  
Stomatogastric Ganglion ◽  
Projection Neurons ◽  
Gamma Aminobutyric Acid ◽  
Stomatogastric Nervous System ◽  
Cancer Borealis ◽  
Excitatory Response ◽  
Commissural Neuron

The multifunctional neural circuits in the crustacean stomatogastric ganglion (STG) are influenced by many small-molecule transmitters and neuropeptides that are co-localized in identified projection neurons to the STG. We describe the pattern of gamma-aminobutyric acid (GABA) immunoreactivity in the stomatogastric nervous system of the crab Cancer borealis and demonstrate biochemically the presence of authentic GABA in C. borealis. No STG somata show GABA immunoreactivity but, within the stomatogastric nervous system, GABA immunoreactivity co-localizes with several neuropeptides in two identified projection neurons, the modulatory proctolin neuron (MPN) and modulatory commissural neuron 1 (MCN1). To determine which actions of these neurons are evoked by GABA, it is necessary to determine the physiological actions of GABA on STG neurons. We therefore characterized the response of each type of STG neuron to focally applied GABA. All STG neurons responded to GABA. In some neurons, GABA evoked a picrotoxin-sensitive depolarizing, excitatory response with a reversal potential of approximately −40 mV. This response was also activated by muscimol. In many STG neurons, GABA evoked inhibitory responses with both K(+)- and Cl(−)-dependent components. Muscimol and beta-guanidinopropionic acid weakly activated the inhibitory responses, but many other drugs, including bicuculline and phaclofen, that act on vertebrate GABA receptors were not effective. In summary, GABA is found in projection neurons to the crab STG and can evoke both excitatory and inhibitory actions on STG neurons.

Biophysical Characterization and Functional Consequences of a Slowly Inactivating Potassium Current in Neostriatal Neurons

1998 ◽  
Vol 79 (4) ◽  
pp. 1989-2002 ◽  
Author(s):  
Lisa A. Gabel ◽  
Eric S. Nisenbaum
Keyword(s):  
Potassium Current ◽  
Time Course ◽  
Voltage Dependence ◽  
Critical Role ◽  
Membrane Potentials ◽  
Resting Potential ◽  
Projection Neurons ◽  
Biophysical Characterization ◽  
Spike Threshold ◽  
Functional Consequences

Gabel, Lisa A. and Eric S. Nisenbaum. Biophysical characterization and functional consequences of a slowly inactivating potassium current in neostriatal neurons. J. Neurophysiol. 79: 1989–2002, 1998. Neostriatal spiny projection neurons can display a pronounced delay in their transition to action potential discharge that is mediated by a slowly developing ramp depolarization. The possible contribution of a slowly inactivating A-type K+ current ( I As) to this delayed excitation was investigated by studying the biophysical and functional properties of I As using whole cell voltage- and current-clamp recording from acutely isolated neostriatal neurons. Isolation of I As from other voltage-gated, calcium-independent K+ currents was achieved through selective blockade of I As with low concentrations (10 μM) of the benzazepine derivative,6 - chloro - 7 , 8 - dihydroxy - 3 - allyl - 1 - phenyl - 2 , 3 , 4 , 5 - tetra - hydro1H-3-benzazepine (APB; SKF82958) and subsequent current subtraction. Examination of the voltage dependence of activation showed that I As began to flow at approximately −60 mV in response to depolarization. The voltage dependence of inactivation revealed that ∼50% of I As channels were available at the normal resting potential (−80 mV) of these cells, but that only 20% of the channels were available at membrane potentials corresponding to spike threshold (about −40 mV). At these depolarized membrane potentials, the rate of activation was moderately rapid (τ ∼ 60 ms), whereas the rate of inactivation was slow (τ ∼ 1.5 s). The time course of removal of inactivation of I As at −80 mV also was relatively slow (τ ∼ 1.0 s). The subthreshold availability of I As combined with its rapid activation and slow inactivation rates suggested that this current should be capable of dampening the onset of prolonged depolarizing responses, but over time its efficacy should diminish, slowly permitting the membrane to depolarize toward spike threshold. Voltage recording experiments confirmed this hypothesis by demonstrating that application of APB at a concentration (10 μM) that selectively blocks I As substantially decreased the latency to discharge and increased the frequency of firing of neostriatal neurons. The properties of I As suggest that it should play a critical role in placing the voltage limits on the recurring episodes of subthreshold depolarization which are characteristic of spiny neurons recorded in vivo. However, the voltage dependence and recovery kinetics of inactivation of I As predict that its effectiveness will vary exponentially with the level and duration of hyperpolarization which precedes depolarizing episodes. Thus long periods of hyperpolarization should increase the availability of I As and dampen succeeding depolarizations; whereas brief epochs of hyperpolarization should not sufficiently remove inactivation of I As, thereby reducing its ability to limit subsequent depolarizing responses.

Dopamine Modulation of Calcium Currents in Pyloric Neurons of the Lobster Stomatogastric Ganglion

2003 ◽  
Vol 90 (2) ◽  
pp. 631-643 ◽  
Author(s):  
Bruce R. Johnson ◽  
Peter Kloppenburg ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Calcium Channel ◽  
Transmitter Release ◽  
Stomatogastric Ganglion ◽  
Calcium Currents ◽  
Voltage Gated ◽  
Pyloric Network ◽  
Pyloric Dilator ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Dopamine Modulation

We examined the dopamine (DA) modulation of calcium currents (ICa) that could contribute to the plasticity of the pyloric network in the lobster stomatogastric ganglion. Pyloric somata were voltage-clamped under conditions designed to block voltage-gated Na+, K+, and H currents. Depolarizing steps from –60 mV generated voltage-dependent, inward currents that appeared to originate in electrotonically distal, imperfectly clamped regions of the cell. These currents were blocked by Cd2+ and enhanced by Ba2+ but unaffected by Ni2+. Dopamine enhanced the peak ICa in the pyloric constrictor (PY), lateral pyloric (LP), and inferior cardiac (IC) neurons and reduced peak ICa in the ventricular dilator (VD), pyloric dilator (PD), and anterior burster (AB) neurons. All of these effects, except for the AB, are consistent with DA's excitation or inhibition of firing in the pyloric neurons. Enhancement of ICa in PY and LP neurons and reduction of ICa in VD and PD neurons are also consistent with DA-induced synaptic strength changes via modulation of presynaptic ICa. However, the reduction of ICa in AB suggests that DA's enhancement of AB transmitter release is not directly mediated through presynaptic ICa. ICa in PY and PD neurons was more sensitive to nifedipine block than in AB neurons. In addition, nifedipine blocked DA's effects on ICa in the PY and PD neurons but not in the AB neuron. Thus the contribution of specific calcium channel subtypes carrying the total ICa may vary between pyloric neuron classes, and DA may act on different calcium channel subtypes in the different pyloric neurons.

scholarly journals Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Matthew CW Oswald ◽  
Paul S Brooks ◽  
Maarten F Zwart ◽  
Amrita Mukherjee ◽  
Ryan JH West ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Neuronal Plasticity ◽  
Second Messengers ◽  
Reactive Oxygen ◽  
Structural Plasticity ◽  
Oxygen Species ◽  
Redox Sensor ◽  
Motor Network ◽  
Network Output ◽  
Activity Dependent

Reactive oxygen species (ROS) have been extensively studied as damaging agents associated with ageing and neurodegenerative conditions. Their role in the nervous system under non-pathological conditions has remained poorly understood. Working with the Drosophila larval locomotor network, we show that in neurons ROS act as obligate signals required for neuronal activity-dependent structural plasticity, of both pre- and postsynaptic terminals. ROS signaling is also necessary for maintaining evoked synaptic transmission at the neuromuscular junction, and for activity-regulated homeostatic adjustment of motor network output, as measured by larval crawling behavior. We identified the highly conserved Parkinson’s disease-linked protein DJ-1β as a redox sensor in neurons where it regulates structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. This study provides a new conceptual framework of neuronal ROS as second messengers required for neuronal plasticity and for network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.

scholarly journals Neuron-class specific responses govern adaptive remodeling of myelination in the neocortex

2020 ◽  
Author(s):  
Sung Min Yang ◽  
Katrin Michel ◽  
Vahbiz Jokhi ◽  
Elly Nedivi ◽  
Paola Arlotta
Keyword(s):  
Critical Role ◽  
Sensory Experience ◽  
Monocular Deprivation ◽  
Fine Tuning ◽  
Initial Increase ◽  
Projection Neurons ◽  
Myelin Sheaths ◽  
Adaptive Circuit ◽  
Callosal Projection

AbstractMyelination plasticity plays a critical role in neurological function, including learning and memory. However, it is unknown whether this plasticity is enacted through uniform changes across all neuronal subtypes, or whether myelin dynamics vary between neuronal classes to enable fine-tuning of adaptive circuit responses. We performed in vivo two-photon imaging to investigate the dynamics of myelin sheaths along single axons of both excitatory callosal projection neurons and inhibitory parvalbumin+ interneurons in layer 2/3 of adult mouse visual cortex. We find that both neuron types show dynamic, homeostatic myelin remodeling under normal vision. However, monocular deprivation results in experience-dependent adaptive myelin remodeling only in parvalbumin+ interneurons, but not in callosal projection neurons. Monocular deprivation induces an initial increase in elongation events in myelin segments of parvalbumin+ interneurons, followed by a contraction phase affecting a separate cohort of segments. Sensory experience does not alter the generation rate of new myelinating oligodendrocytes, but can recruit pre-existing oligodendrocytes to generate new myelin sheaths. Parvalbumin+ interneurons also show a concomitant increase in axonal branch tip dynamics independent from myelination events. These findings suggest that adaptive myelination is part of a coordinated suite of circuit reconfiguration processes, and demonstrate that distinct classes of neocortical neurons individualize adaptive remodeling of their myelination profiles to diversify circuit tuning in response to sensory experience.

Abstract 87: The Accumulation of Myeloid-derived Suppressor Cells Is a Compensatory Response to the Development of Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Xiao Z Shen ◽  
Peng Shi ◽  
Jorge Giani ◽  
Ellen Bernstein ◽  
Kenneth E Bernstein
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Angiotensin Ii ◽  
Critical Role ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Compensatory Response ◽  
Immunosuppressive Cell ◽  
Induced Hypertension

The immune system plays a critical role in the development of hypertension. The immune response consists of pro-inflammatory cells, but also immunosuppressive cells that reduce T cell function. An important category of natural immunosuppressive cell is myeloid-derived suppressor cells (MDSC). We now show that blood and spleen CD11b+ Gr1+ myeloid cells are elevated 2-fold in both angiotensin II and L-NAME induced hypertension. These increased myeloid cells are MDSC in that they elevate IL-4R expression and suppress T cell proliferation. When hypertensive mice were depleted of MDSC, using either anti-Gr1 antibody or gemcitabine, there was a 15 mmHg rise in blood pressure and aggravation of T cells activation with increased production of IFN-γ, TNFα and IL-17 in both spleen and kidney. In contrast, adoptive transfer of MDSC reduced blood pressure in angiotensin-II induced hypertension by 25 mmHg (see Figure). These data suggest a new concept, that the accumulation of MDSC is a compensatory response to the inflammation induced by hypertension. They also indicate that MDSC play an important role in regulating blood pressure.

scholarly journals Featured Article: The loss of copper is associated with the increase in copper metabolism MURR domain 1 in ischemic hearts of mice

2018 ◽  
Vol 243 (9) ◽  
pp. 780-785 ◽  
Author(s):  
Kui Li ◽  
Chen Li ◽  
Ying Xiao ◽  
Tao Wang ◽  
Y James Kang
Keyword(s):  
Myocardial Ischemia ◽  
Normal Level ◽  
Time Course ◽  
Critical Role ◽  
Copper Metabolism ◽  
Serum Copper ◽  
Ischemic Myocardium ◽  
Ischemic Heart ◽  
Coronary Artery Ligation ◽  
Artery Ligation

The distribution of copper (Cu) in the biological system is regulated by Cu transporters and chaperones. It has been known for a long time that myocardial ischemia is accompanied by the loss of Cu from the heart, but the mechanism by which this occurs remains unknown. The present study was undertaken to understand the relationship between Cu loss and alterations in Cu transporters during the pathogenesis of myocardial ischemia. Male mice (C57 BL/6J) were subjected to left anterior descending (LAD) coronary artery ligation to induce myocardial ischemia. Changes in Cu concentrations in serum and hearts were determined from blood and tissue samples harvested at different time points for a total of 28 days after the operation. Cu concentrations in the ischemic myocardium were continuously decreased starting at the fourth day after LAD artery ligation, gradually depleted by more than 80% of the normal level at the 10th day, and remained at the lowest level (about 20% of normal levels) thereafter. Serum Cu concentrations were correspondingly increased starting at the fourth day, reached to the highest level between day 7 and 10, and gradually recovered to the normal level until 21st day after the operation. Along with the same time course, the intracellular Cu exporter copper metabolism MURR domain 1 (COMMD1) was significantly and sustainably increased, but ATP7A and ATP7B were not significantly changed in the ischemic myocardium. These results suggest that during the pathogenesis of myocardial ischemia, COMMD1 would play a critical role in exporting Cu from the ischemic myocardium to the blood. Impact statement In this work, we found that copper efflux from the ischemic heart leads to the elevation of serum copper concentrations, addressing a long-term question related to serum copper elevation in myocardial ischemia patients. The efflux of copper from the ischemic heart results at least in part from the upregulation of copper metabolism MURR domain 1 (COMMD1) in the heart upon ischemic insult. This work provides a novel insight into copper homeostasis and alteration in cardiovascular system.

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