AKIRA

Interesting SfN posters

2012-01-02T15:00:00.000-05:00

It is a bit late but this is about the SfN meeting. During cleaning up my desk near the end of year I rescued a bunch of notes I took during the meeting. Most of them were hard to read. Here are some.

497.06 Presentation Title: Endogenous neuropeptide facilitates INap pacemakers and acts on low respiratory frequency
*A. DOI, J. M. RAMIREZ

I often heard of Dr. Doi's work in Dr. Ramirez's talks. This was actually my first time visiting his poster. He explained to me in very clear logic in English and then we chatted in Japanese. He studied the role of endogenous substance P (SP) and toic activation of neurokinin1 (NK1) receptors in the generation of eupneic respiratory rhythm in pre-Bötzinger complex (pre-BötC) by blocking of NK1 receptors.
Both Cd²⁺-sensitive (CS) and Cd²⁺-insensitive (CI) pacemakers received endogenous SP release, but CI pacemaker activities were only tonically facilitated by activation of NK1 receptors. This seems to be due to the difference in voltage-sensitivity between CS pacemakers and CI pacemakers. The former mediated by non-selective cation channel (ICaN) whereas the latter by persistent Na⁺ channel (INaP).

585.09 Presentation Title: Electrical coupling in Aplysia bag cell neurons: Biophysical characterization and role in synchronous firing.
P. L. W. COLMERS, *N. S. MAGOSKI
The role of gap-junctions among the Aplysia bag cell neurons were examined. Meclofenamic acid is an electrical coupling blocker.

699.20 Presentation Title: Developmental reconfiguration of gaze control commands from spinal locomotor circuitry during Xenopus metamorphosis.
*D. COMBES, G. VON UCKERMANN, D. LE RAY, F. LAMBERT, H. STRAKA, J. SIMMERS
Dr. Denis Combes' poster is always one of my favorite in this meeting. This is a true NEUROBIOLOGY work. He studied the developmental changes in the neural control of eye movement in tadpole. During metamorphosis, Xenopus switches its mode of locomotion from tail-based undulatory movements to bilaterally-synchronous hindlimb kick propulsion, with intervening stages where these two modes co-exist.
There is a developmental transition in spinal efference copy control of extraocular motor output during Xenopus metamorphosis that corresponds to the change in locomotor strategy.

818.15 Evolution of a behavior mediated by the lateral line system adapts Astyanax to life in darkness.
*M. YOSHIZAWA, W. R. JEFFERY
This is also a very interesting work that grasped the moment of evolution of cavefish traits during the adaptation processes. Showing physiological and genetic basis of an adaptive behavior, vibration attraction behavior (VAB) inAstyanax mexicanus, which has an eyed surface (surface fish) and a blind cave (cavefish) dwelling forms.
Quantitative laboratory assays indicate that VAB is common in cavefish but rarely observed and much less robust in surface fish. VAB is beneficial for feeding in the dark. Increase in superficial neuromast (SN) during development is important forVAB.

Aplysia brasiliana

2011-06-10T11:17:00.009-04:00

Charuni, a grad student in our lab, is now studying the swimming behavior of a sea hare, Aplysia brasiliana. Compared to other sea slugs, this one looks very intelligent. Especially when they are swimming. Peeping over the water, flipping over, making quick turns... They are not sluggish at all. Their playful behaviors make me even think like these creatures are almost as intelligent as dolphins.

The Dendronotus and Melibe paper in Current Biology

2011-05-28T12:23:00.009-04:00

My latest paper appeared in Current Biology!

Different Roles for Homologous Interneurons in Species Exhibiting Similar Rhythmic Behaviors

This paper describes the differences in synaptic properties and organization of the swim CPGs in closely-related nudibranch species, Melibe leonina and Dendronotus iris. These animals show very similar swimming behaviors with left-right body flexions. However, their CPGs have quite different network organization; they have different synaptic connectivity and responded differently when perturbed by current injections. Thus, similarity in species-typical behavior is not necessarily predictive of common neural mechanisms.

We also discuss about how species-specific behaviors have developed through the animal evolution. We showed that, even though closely-related animals with similar neuronal architectures exhibit similar behaviors, some degree of divergence can be found in the underlying neural circuitry. A pair of homologous neurons in one species have regulatory role to modify the motor rhythm, whereas in the other species they are part of the CPG and reinforce the rhythm regularity. We don't know what is the functional significance; maybe such difference will be hidden until some time when it becomes more critical in the face of some environmental perturbations.

Plateau potentials in sacrocaudal motoneurons of chronic spinal rats, recorded in vitro

2011-05-03T00:57:00.004-04:00

David J. Bennet, Yunru Li, and Merek Siu
J. Neurophysiol. 86, 2001

Jerky limb movements often develop after spinal cord injury. This general spasticity syndrome is caused at least in part by enhanced plateau potentials in the MNs. Depolarization in MN triggers the plateau potential and causes its sustained firing, which lead to exaggerated muscle contraction. This paper describes the basic properties of this plateau potential and the sustained firing in MNs after spinal cord transection. The recurrent GABAergic and Glycinergic inhibitions may play a role in suppressing this enhanced plateau potential. This will be studied in following paper.

A new pump from Pentair Aquatics

2011-04-23T09:34:00.011-04:00

A few weeks ago on Saturday I installed a new pump in one of our animal tanks. It is Quiet One Aquarium Pump 3000 - 780 gph from Pentair Aquatics. It can directly connect to Lifegard Module Filter System. But I didn't do that. I didn't want to do the plumbing job for all the circuitry of the PVC pipes under the tank on weekend. I just used plastic tubes to put it in.

Little Giant pumps were originally installed when Paul purchased them in 1997. Since then we had been using them with no specific reason despite their frequent failures. I like this new one better. It's real quiet. It is waterproof. And it's cheap (~$60)! Little Giant pumps usually cost more than $200. I will switch from Little Giant to Quiet One for all tanks.

Dendronotus swim movie

2011-04-02T01:20:00.003-04:00

OK, this is another nudibranch, Dendronotus iris.

Just like Melibe, it swims by lateral body flexions.

Swimming Melibe leonina

2011-03-26T00:17:00.006-04:00

Melibe leonina swimming in a glass tank.

Shooting a movie is tough!
To make this, I spent 2 days in the tank room and 2 nights on computer.

次世代エネルギーはどんなものか

2011-03-25T20:21:00.009-04:00

　いま話題の原子力発電も，火力発電も，水力発電も，風力発電も，地熱発電も，波力発電も，磁石とコイルからなるモーターを回転させることによっておこる　『電磁誘導』　によって電気をつくり出しているという点では同じである
　唯一の例外は太陽電池だろう
　太陽電池は，光がモノに当たったときに放出される光電子を集めて，それを電流にしている
　いずれの方法も，エネルギー変換の効率は，すこぶる悪い

　これら人間の手によるエネルギー変換と比べたとき，それらをはるか凌ぐ高効率のエネルギー変換が生物の細胞内で起こっている
　植物の葉緑体では　『光合成』　によって太陽光を炭水化物の化学エネルギーに変換しているし，一方，ミトコンドリアでは　『呼吸』　によって有機物に蓄えられた化学エネルギーを，より利用しやすいリン酸化合物の化学エネルギーへと変換している
　また，呼吸も，光合成も，膜のプロトン濃度勾配という電気エネルギーによって仲介されているという点で似ている
　呼吸でつくり出された化学エネルギーは，細胞内外のタンパク質の形を変化させ，最終的には筋の収縮や細胞膜の電気現象をひき起こす

　次世代のエネルギーの開発というのは，新しいエネルギー源を見つけるというより，むしろ我々が入手できるエネルギーをいかに効率よく電気エネルギーに置換するかという点に絞られるんじゃないだろうか
　おそらくそれは従来の磁石とコイルを使ったものではなく，むしろ上記の光合成や呼吸にみられるような生体内のエネルギー変換機構を巧みに利用するか，あるいはそれと似たものを人為的に作りだすことによってもたらされるんじゃないかと思うがどうだろう

　

Happy birthday Paul!

2010-11-07T01:39:00.006-04:00

It's good to have girls in the lab.
I really thought so when I heard Charuni and Ariana laughing at something about the birthday cake while putting letters on it. I don't know what they were laughing at, but I liked it.

Paul became 50. I am 10 years behind.
He was 41 and I was 31 when I came here. I remember Stefan was 38. Jim was 34.
Now he is 50 and I am 40.

Last week, he said I was doing well on getting good data.
Well, getting new data is like breathing to me.

Dissecting a Little Giant

2010-09-13T21:59:00.009-04:00

We use Little Giant Pumps for animal tanks. This pump looks sturdy, but often fails if you don't lube it like every 6 months or so like Harley Davidson. You have to baby-sit it all time. Just like HD, this Little Giant is proudly made in USA.
By the way, Georgia Aquarium uses Iwaki pump, which is more like Honda than Harley Davidson.

Today, I had to shut down one of our tanks to replace the filter. Then, this little giant failed to restart.
So I had to restore it.

This is a tricky part. You need a flat-head screwdriver and a hammer to remove this flip thing.

Water propeller, Motor, Inlet-outlet part, main shaft with fan, end cover, magnet ring

Inside the motor. This needs overall cleaning.

Cause of voltage drifting

2010-09-11T22:14:00.005-04:00

Sources of 60 Hz noise can be detected by a piece of tin foil.
Don't forget connecting it to reliable ground.

Drifting of the bath potential level is also a quite common problem.
If it is minor one, you can try re-chloriding the silver wires for the bath ground and for electrodes.

If drift goes by several hundred mV, then it is not just a chloriding issue.
There must be electrical connection between the dish saline and surrounding metallic devices. This happens after saline overflow and spill.
The ground for the amplifier head stage (bath ground) and that for other electrical devices (device ground) are not exactly the same. If the dish saline was connected to both of these grounds, then there would be a voltage drop (= drift).

The joint between the silver wire and the soldered point can produce a strong voltage when it gets wet just like a voltaic cell. The ground wire often sucks up saline and gets wet. If the saline reach the soldered joints, it will cause a huge drift. Do not use a short silver wire for grounding the dish. Keep them dry all time during e-phys experiment.

New Lab

2010-06-11T00:24:00.008-04:00

We, Katz lab, and the Neuroscience Institute have moved to the new building near Georgia State MARTA Station.
We are on the 8th floor.

Cool-looking building. Tornado-proof? Probably not.

My rig room has a window. I can see the horizon while poking cells!

Our aquarium is now 30 sec away from the lab. This is great.
I did lots of plumbing work to install new filtering system and protein skimmers. This is a hard work. I have had 3 leakage from various PVC joints I made. One of them was due to a crack that was developed during weekend. By Monday morning, half of the tank water leaked out.

One of the chillers failed because the compressor overload protector had fallen off and disconnected the power. I opened it up the chiller and rewired the circuit to skip this failed protector. Now it is running fine.

I was also in panic when I found the other chiller heated up in the morning. The radiator fan was not running. The water was like hot tub. I opened the chiller and found that the fan blade was stuck by touching the frame. I mended it back and now its working fine like new.

Setting up the aquarium is like buying a new Harley Davidson. You will have trouble after trouble until the machinery gets settled.
I would definitely buy Honda.

Backfill

2010-01-28T12:54:00.009-05:00

I did backfills on two Melibe brains. Both appeared very nicely.

My success rate on backfilling is pretty high, almost 100%.
It is simple. All you have to do is to let dye solution touch only the cut end of the nerve you want to fill. And make sure the prep is in healthy condition until fixation. Poor results are mostly due to failure in these two things. It is not because of materials or protocols. It is how you manipulate them.

Insights into a molecular switch that gates sensory neuron synapses during habituation in Aplysia

2009-11-25T01:34:00.007-05:00

Tony D. Gover, Thomas W. Abrams

I think this paper spends so much space and time only to deny depletion hypothesis.
The effects of calpain and Arf sound very interesting and promissing.

1. Habituation of reflex responses in vertebrates and invertebrates: a simple form of neural plasticity
In addition to habituation, the repeated stimulus may lead to a strengthening of the response, known as sensitization.
Their observations led them to propose the ‘‘dual-process theory” in which the behavioral change actually reflects the
contribution of these two independent processes.

Whereas short-term depression at these synapses appears to be mediated entirely by presynaptic changes (Castellucci & Kandel, 1974; Manseau, Fan, Hueftlein, Sossin, & Castellucci, 2001), long-term depression that is initiated by extensive stimulation or blocks of stimuli delivered over hours appears to depend upon signals initiated by postsynaptic glutamate receptors, including Ca2+ influx through NMDA receptors (Lin & Glanzman, 1996; Mata, Chen, Cai, & Glanzman, 2008) (see also Ezzeddine & Glanzman, 2003).

2. Mechanisms of synaptic depression in other systems

2.1. Depletion of the readily releasable pool of vesicles as a mechanism of depression
Historically, the earliest proposed mechanism for synaptic depression was depletion of the neurotransmitter that is available for release. Vesicles at synaptic release sites that are available for immediate release are considered to constitute a readily releasable pool (Betz, 1970; Gingrich & Byrne, 1985; Stevens & Tsujimoto, 1995); these vesicles may already be docked at exocytosis sites.

2.2. Use-dependent inactivation of presynaptic Ca2+ channels

2.3. Desensitization of postsynaptic receptors

2.4. Autoreceptors and retrograde signaling
At parallel fiber-to-Purkinje cell synapses in cerebellum, high frequency presynaptic activity causes suppression of transmitter release, which is mediated by release of endocannabinoids from the postsynaptic Purkinje cell; the endocannabinoids act on receptors on presynaptic terminals, resulting in reduced Ca²⁺ influx (Brown, Brenowitz, & Regehr, 2003).

3. Proposed mechanisms for synaptic depression at the sensory neuron-to-motor neuron synapse in Aplysia
3.1. Short-term homosynaptic depression at sensory neuron-to-motor neuron synapses involves a presynaptic mechanism, rather than alteration in postsynaptic responses

3.2. Ca2+ current inactivation
With repeated stimulation of the sensory neuron, the action potential duration decreased, suggesting that Ca2+ influx decreased with each successive action potential. Klein et al. (1980) also measured the Ca²⁺ current in
the soma of the presynaptic sensory neuron under voltage clamp.
With repeated depolarizing voltage steps, they observed that the Ca²⁺ current decreased in parallel with the decline in the amplitude of the EPSP recorded in the motor neuron.
Gingrich and Byrne (1985) also reached the conclusion that Ca²⁺ current inactivation alone during the normal duration ac-tion potential does not account for depression at this synapse.

Armitage and Siegelbaum (1998) used fluorescent Ca²⁺ indicators to directly measure Ca²⁺influx at presynaptic varicosities of sensory neurons through the dihydropyridine-insensitive Ca²⁺ channels. No change in Ca²⁺ influx through these channels that initiate release was observed during synaptic depression.

3.3. Depletion of the readily releasable pool of vesicles as the primary mechanism for synaptic depression during habituation
Thus, depletion of the readily releasable pool of vesicles can contribute to depression, but probably only with relatively prolonged presynaptic activity.
Recent evidence implicated the Ca²⁺-activated protease calpain both in modulation of depression at the sensory neuron-to-motor neuron synapse and in serotonin-induced facilitation after depression (Khoutorsky & Spira, 2005).
This intriguing observation has been interpreted to indicate that this protease acts to untether vesicles in the reserve
pool, and thereby initiates mobilization of vesicles to the readily releasable pool. Although this is a plausible model, another possible function for calpain is the proteolytic cleavage of protein kinase C (PKC), converting the enzyme to the persistently active PKM form (Sutton, Bagnall, Sharma, Shobe, & Carew, 2004). PKC is known to participate in facilitation of depressed sensory neuron-to-motor neuron synapses by serotonin (Ghirardi et al., 1992; Manseau
et al., 2001), and also acts to prevent the development of depression during bursts of activity (see below). Thus, calpain cleavage of PKC could reduce synaptic depression.

3.4. Switching of release sites to a silent state as a mechanism of synaptic depression

Gover et al. (2002) considered five mechanisms of synaptic depression:
(1) vesicle depletion, which by default must be dependent on vesicular release (Fig. 3);
(2) reduction in the probability of release of individual releasable vesicles after a release event;
(3) reduction in the probability of release of individual releasable vesicles after an action potential, but independent of a release event;
(4) silencing of release sites after a release event, and
(5) silencing of release sites, after an action potential, but independent of a release event (Fig. 4).

These data suggest that the probability of release does not change gradually; rather individual release sites are simply silenced, or switched off, during development of depression.
Furthermore, Royer et al. (2000) argued that given their data, if p were nonuniform across release sites, then homosynaptic depression due to silencing of release sites would be independent of release [which is consistent with the conclusions of Gover et al. (2002)].

3.5. Other evidence suggesting depletion of vesicles is not the major mechanism for synaptic depression at Aplysia sensory neuron synapses

4. Evidence from other systems suggesting that vesicle depletion is not the primary mechanism responsible for synaptic depression
Rather depression with relatively few stimuli or with low frequency stimulation cannot be explained primarily by depletion.

5. Ca²⁺ influx initiates the silencing of release sites during depression at sensory neuron-to-motor neuron synapse in Aplysia
In the absence of Ca²⁺ influx no detectable synaptic depressin developed. Thus the switching off of sensory neuron release sites during repetitive presynaptic activity appears to be initiated by presynaptic Ca²⁺ influx.

6. The switch that silences sensory neuron-to-motor neuron synapses during depression in Aplysia involves the small G protein Arf
One possibility is that because facilitation of depressed synapse involves protein kinase C (Ghirardi et al., 1992; Manseau et al., 2001), the switching of synapses to a silent state is mediated by a protein phosphatase. Indeed, some types of long-term depression involve protein phosphatases (...).

... a general inhibitor of Arf signaling powerfuly inhibited transmission at sensory neuron-to-motor neuron synapses and occluded the development of synaptic depression. Similarly, a binding domain of an Arf effector protein acted as a dominant negative and substantially reduced the depression that developed with single action pontentials. Reciprocally, we found that constitutively active Arf6, when injected into presynaptic sensory neurons, prevented the development of synaptic depression.

7. Bursts of sensory neuron activity prevent the development of homosynaptic depression"burst-dependent protection" from synaptic depression
Burst-dependent protection from synaptic depression involves Ca²⁺-dependent activation of protein kinase C (PKC). Chelating Ca²⁺ in the presynaptic sensory neuron with intracellular EGTA, which is not a sufficiently rapid buffer to block transmitter release, eliminates burst-dependent protection.

The recovery paper

2009-10-15T21:20:00.008-04:00

My latest paper will appear in the Journal of Neuroscience.
October 21, 2009 | Volume 29 | Number 42 |

They will introduce my paper in "This Week in The Journal"
Development/Plasticity/Repair - "Nerve Transection Induces Circuit Reorganization in Tritonia"

The article title is:
"Functional Recovery after Lesion of a Central Pattern Generator"
by Akira Sakurai and Paul S. Katz

In this paper, we found that severing a set of connections between some CPG neurons impaired motor pattern production but that the system spontaneously recovered over the course of a few hours to a day. Furthermore, we observed corresponding changes in synaptic strength that can account for the functional recovery.

Neuromodulation of motor systems

2009-10-14T23:30:00.004-04:00

Among many reviews about CPG funciton, I like this one by Ole Kiehn and Paul S. Katz.
The introduction starts with a brief talk about dancing.

"...by changing cellular and synaptic properties, neuromodulators choreograph circuits from an ensemble of interacting neurons capable f dancing with a variety of partners."

2. The elements of neuromodulation in motor systems: alterations of cellular and synaptic properties
The CPGs - Localized neuronal networks in the central nervous system control the timing of the coordinated muscle activities, capable of producing rhythmic movement even when isolated from the sensory input (Delcomyn 1980).

The CPG function depends on synaptic interconnections and intrinsic membrane properties.
Neuromodulation changes both of them.

1) Rewiring circuits
We may often think of the nervous system as a hard-wired device whose connectivity is changed only during the developental period or as a result of learning.
NO, the strength of connections between neurons is not fixed, but can vary continusously under moment-to-moment neuromodulatory control.
The wiring diagram for a circuit is merely an outline of potential connections and does not uniquely determine the flow of information at all times.
- Modulation of chemical transmission
The effect of neuromodulation can be a functional disconnection of cells or a strengthening of the communication between cells.
Thus, the wiring diagram of synaptic connections is strongly dependent upon which neuromodulator is present.
In vertebrate locomotion, 5-HT and noradrenaline modulate glycinergic synapses to increase circuit flexibility.
- Modulation of electrical coupling

2) Changing neuronal personalities

- Modulation of resting conductances can determine neuronal participation in a network

- Modulation of conductances involved in phase transisions

- Modulation of conductances that determine spike rate

- Modulation of conductances underlying neuronal bistability

- Modulation of conductances underlying conditional bursting

3) Changes in cellular and synaptic properties produce secondary effects

The differential actions of neuromodulators on neurons in motor circuits underlie some forms of behavioral plasticity such as motor pattern selection.

3. Choreographing motor patterns: the effects of neuromodulators on the output of motor circuits

Neuromodulatory substances can initiate motor patterns by endowing neurons with the properties that are needed to form a functional CPG circuit.
Neuromodulatory sunstances can alter (or reorganize) motor patterns by changing those properties.

1) Neuromodulators can activate motor patterns
As a rule, the initiation of rhythmic movements requires non-rhythmic input from a source external to the CPG network itself.
-fast synaptic input (tadpole escape)
-neuromodulatory input (Tritonia swim, cats, rats, rabbits)

2) Neuromodulators can alter ongoing motor activity
- changing the speed/frequency
- muscle force
- phase relationship

3) Neuromodulators can reconfigure networks
-stomatogastric system
- At the moment, little is known about these types of network reorganizations in CPGs other than those in the stomatogastric system. Reconfiguration in the larger neuronal networks that control thythmic activity in vertebrates is difficult to evaluate because the CPG networks are poorly difined and it is impossible to be sure that one has recorded from all possible members of a functional circuit.

4) Neuromodulation can alter the ability of a CPG to drive its follower motor neurons

4. INtegrating neuromodulation into neuronal circuits

1) Properties of neuromodulatory neurons

2) Sources of neuromodulation
- Extrinsic vs Intrinsic

3) Convergence of modulation

5. Long-term alteration of motor patterns
Fast proprioceptive adjustment mechanisms are plastic and that they can adjust to long-term changes in the sensory signaling.

- in spinalized cats where locomotion on a treadmill is evoked by L-DOPA injection, cutting the lateral-gastrocnemius-soleus nerve results in long-term up-regulation of the load-compensating effects from group I afferents in the synergistic medial-gastrocnemius nerve, allowing the cat to slowly recover its normal stepping behavior (Whelan and Pearson 1997).

Neuromodulatory inputs may play a role in promoting long-term plasticity of CPG circuits. In spinalized cats, daily intraperitoneal or intrathecal injections of the alpha-2 adrenergic receptor agonist, clonidine, enhanced the recovery of locomotion when combined with training on a treadmill (Chau et al., 1998).

Melibe leonina

2009-10-09T10:54:00.006-04:00

I am working on Melibe brain now. It is so small.

There are two small ganglia on Pleural-Pleural connective nerve. What they do?
A copepod is sitting on the brain in the dish. I think it came out from the stomach, but it is still alive. It is so pity that I have to kill it to protect my prep.

I saw a pair of green tube that seem to go to the dorsal gill from the stomach.
Is it also solar-powered?

Long-Term Modifications in Motor Cortical Dynamics Induced by Intensive Practice

2009-10-08T09:06:00.002-04:00

Bjørg E. Kilavik, Sébastien Roux, Adrián Ponce-Alvarez, Joachim Confais, Sonja Grün, and Alexa Riehle

The timing of the task is represented in the temporal structure of significant spike synchronization at the population level. By practice, the temporal structure of synchrony was shaped. Synchrony became stronger and more localized in time during late experimental sessions, in parallel with a behavioral improvement, whereas the firing rate in the same neurons mainly decreased.

The brain processes in parallel sensory, temporal, and contextual information, which has to be combined appropriately to organize a movement.

It is widely accepted that sensorimotor funcitons are based on activity modulations in neuronal networks distributed over various brain structures. (Wise, 1984; Tanji and Kurata 1989; Riehle, 2005).
The timing of modulation of synchrony and firing rate at the population level in motor cortex suggests that synchrony may be preferentially involved in early preparatory and cognitive processes, whereas rate modulation may rather control movement initiation and execution (Riehle et al., 2000; Grammont and Riehle, 2003).

Re-expression of Locomotor Function After Partial Spinal Cord Injury

2009-09-03T10:32:00.002-04:00

S. Rossignol, G. Barrière, O. Alluin and A. Frigon

The CPG is defined as a spinal network of neurons capable of generating a rhythmic pattern consisting of alternating activity between flexor and extensor motoneurons on the same side with reciprocal activation of homologous motoneurons in the other limb of
the same girdle. In general, during walking or trotting, this network ensures that flexor motoneurons on one side are active with contralateral extensors and vice versa for extensor motoneurons.

...In such a preparation, rhythmic activity, evoked by injecting the noradrenaline precursor l-dihydroxyphenylalanine (L-DOPA), is recorded from peripheral muscle nerves and is termed “fictive locomotion.”

...Indeed, electrical stimulation of a circumscribed brain stem region called the mesencephalic locomotor region (MLR), ... Various gait patterns, such as walk, trot, and gallop, can be
evoked with increasing stimulation intensity.

...Other descending pathways release specific neurotransmitters, which are synthesized by cells in well defined brain stem nuclei (e.g., noradrenaline in the locus coeruleus and serotonin in the raphe and parapyramidal nuclei). These neurotransmitters exert powerful effects on the spinal circuitry and can change characteristics of the locomotor pattern.

...it is important to know that, after a complete spinal transection, most quadruped mammals will
recover some degree of locomotor function in the limbs below the lesion. Cats, rats, and mice can re-express hindlimb locomotion provided the spinal cord below the complete lesion is properly
stimulated, either pharmacologically or through locomotor training.

...locomotion is controlled at multiple levels of the central nervous system, and a subtle and intricate balance is established between these levels of control. This then leads to the question of how an optimal equilibrium is re-established when this exquisite balance is perturbed following lesions of the spinal cord.

...Instead of taking over lost spinal functions, remnant descending pathways or regenerating pathways could direct the reorganization of the spinal circuitry so that it can function optimally and with a greater level of independence so that, after the complete section, the full pattern of hindlimb locomotion can be expressed by an already autonomous CPG.

The main conclusion of this brief review of multiple types of lesions is that there are several ways through which the CNS and peripheral afferent inputs can access the spinal locomotor circuitry. This apparent redundancy points to the fact that the rhythm is generated at the spinal level and that various degrees of control levels can modulate this spinal circuitry through multiple pathways. The removal of certain pathways produces specific locomotor deficits, but the
spinal circuitry and other intact pathways are still able to optimize remnant locomotor functions.

Prominent Role of the Spinal Central Pattern Generator in the Recovery of Locomotion after Partial Spinal Cord Injuries

2009-09-03T10:22:00.002-04:00

Grégory Barrie`re, Hugues Leblond, Janyne Provencher, and Serge Rossignol

The general accepted model of locomotor control is tripartite.
1) CPG
2) sensory feedback
3) descending pathways

After partial spinal cord injury (SCI), this optimal balance is perturbed because communication between the brain and the spinal CPG is altered (Barbeau and Rossignol, 1994).

Q: Are there lastic changes within descending pathways?
Or, the spinal CPG retains its function and that changes in descending commands aim at maintaining an optimal control of the spinal locomotor network?

The role of the CPG in the recovery of locomotion after incomplete spinal cord lesion is mostly unknown.

RESULT
The first step consisted of an incomplete section of the spinal cord at the thoracic level T10 or T11.
The second step was a complete transection of the spinal cord at T13 or L1.

1) The recovery of quadrupedal locomotion after partial lesions is mostly the result of an intrinsic reorganization of the spinal locomotor network below the lesion.

2) Locomotor training is a major factor in facilitating the recovery process because cats intensively trained after the partial lesion expressed a very high locomotor
performance bilaterally within hours of the complete spinalization, whereas in untrained animals only a unilateral locomotion was observed in the limb ipsilateral to the partial lesion.

3) Plastic reorganization of the spinal CPG may still occur after the complete spinal section because bilateral locomotor performance improved with training over time in all cats after complete spinalization.

Altogether, this work highlights the importance of promoting spinal neuroplasticity in rehabilitation strategies in SCI patients, especially to maintain the spinal circuitry in an optimal condition to generate locomotion.

Conversation with the e-phys master

2009-08-24T18:25:00.014-04:00

Mater: Poke it....

Young Akira: ?

Mater: I said, poke it!

Young Akira: .... (Tap, tap)

Master: Wah was dat? An exhibition? We need EMOTIONAL CONTENT. Try again!

Young Akira: .... (TAP, TAP)

Master: I said EMOTIONAL CONTENT. Not anger! Now, try again!
With meeee!

Yong Akira: .... (Tap! Tap!)

Master: Ho, ha! That's it! See, it's bursting! How did it feel to you?

Young Akira: Well, let me see...

Master: (Whap!) Don’t think! FEEEEEL. It is like a finger pointing a way to the neuron!
(Whap!) Don’t concentrate on the electrode or you will miss all that heavenly action potential! Do you understand?

Young Akira: I see, sir... (Bows)

Master: (Whap!) Never take your eyes off your prep!

Prolonged presynaptic posttetanic cyclic GMP signaling in Drosophila motoneurons

2009-08-21T09:21:00.008-04:00

By Dinara Shakiryanova and Edwin S. Levitan
PNAS 105 (36): 13611-13613

1) The activity of cyclic nucleotide activity is first shown at the terminal. It is cGMP, not cAMP.
2) NO generation and activation both occur in the presynaptic terminal
3) It is surprisingly long lasting.

FRET-based cAMP imaging showed a Ca-dependent sustained increase of cAMP (or cyclic nucleotide) after a brief activation of synapse (fly neuromuscular synapse).

However,
1) Ca-dependent increase of cyclic nucleotide (cAMP). Both extracellular and RyR-mediated.
But,
- Ca-stimulated AC mutant has no effect.
- cAMP-specific PDE mutant has no effect.

2) This is cGMP instead of cAMP?
- GC inhibitor (ODQ) reduced the FRET signal.
- NOS inhibitor and NO scavenger reduced it too.
- Expression of cGMP-specific PDE shortened the signal.
- IBMX indeed extend the cGMP signal duration.

NOS-guanylyl cyclase-mediated presynaptic cGMP synthesis.

ODQ: guanylyl cyclase inhibitor
L-NAME: NOS inhibitor
PTIO: NO scavenger

They don’t show the effect on synaptic strength…