Synaptic Bombardment Modulates Muscarinic Effects in Forelimb Motor Cortex

Niraj S. Desai and Elisabeth C. Walcott

Continuous synaptic bombardment with a complex barrage of excitatory and inhibitory inputs alter many aspects of neuronal responsiveness (by depolarizing neurons, increasing membrane conductance, and introducing fluctuations). This study shows how it shapes neuromodulation of postsynaptic responses by examining muscarinic modulation of forelimb motor cortex, a brain area in which cholinergic stimulation is known to be necessary for modifications during motor skill learning. Using a dynamic clamp system to inject simulated conductances
into pyramidal neurons, they mimicked in vivo-like activity by introducing a random background of excitatory and
inhibitory inputs. The presence of such background conductances strongly attenuated most muscarinic neuromodulatory effects, with the notable exception that sustained firing responses to trains of inputs were well preserved. This may be important for promoting plasticity in vivo.

The Journal of Neuroscience, February 22, 2006 • 26(8):2215–2226


Similar thing may be happening in the slug's CPG in the sea water. Most of my experiments testing neuromodulation have been done in HiDi saline, which suppresses anonymous synaptic bombardment.

Neurotrophins mediates a rapid switch in transmitter release

Bo Yang, John D. Slonimsky and Susan J. Birren

Brain-derived neurotrophic factor (BDNF) altered the neurotrasmitter release properties of sympathetic neuron-myocyte connections in rodent cell culture, leading to a rapid shift from excitatory norepinephrinic transmission to inhibitory cholinergic trasmission.

p75 neurotophin receptor mediates modulation of release of distinct neurotransmitter pools, resulting functinoal switch between excitatory and inhibitory neurotoransmission in individual neurons.

Nature Neuroscience 5(6) 539-545 (2002).

From IPSPs to EPSPs: Transition to seizures in the mouse hippocampus

Transition to seizures in the isolated immature mouse hippocampus: a switch from dominant phasic inhibition to dominant phasic excitation.
M. Derchansky, S. S. Jahromi, M. Manami, D.S. Shin, A. Sik, and P. L. Carlen

Neuronal networks can display non-linear complex behaviours that result in multiple stable states, with the capacity to undergo spontaneous transition between these states. An in vitro model of temporal lobe epilepsy (TLE) generates recurrent seizure-like events. The authors studied the sequence of inhibitory and excitatory events during the preictal state.

In animal models of epilepsy, dendritic but not somatic GABAergic inhibition is decreased and it has been hypothesized that this is the mechanism responsible for ictal generation.
Anothor hypothesis for ictal generation is that interneurons might be involved in synchronizing large neuronal populatios. This synchronization is possible by their abundant connectivity to pyramidal cells. Excitation might be achieved by the alteration of the intracellular chloride gradient after prolonged high-frequency activation of GABA-A receptor.


During the preictal state, there was a total reversal in the polarity of the synaptic potentials in pyramidal cells, fast-spiking cells, and non-FS cells.

The hyperpolarizing potentials during preictal state are generated by recurrent IPSPs (Cl-).
However, the reversal is not due to the change in the reversal potential for Cl ion. The authors suggest that the excitatory drive was produced by a complex change in the synaptic interactions among pyramidal cells and interneurons.

J. Physiol. 586.2, 477-494 (2008).

Economodulation

Stock price is going up for several days in a row.
I am hoping it is not short-term like PTP, but rather it continues for a longer term like LTP.

I know that just a single bad news can negate this sustained increase and immediately brings it down to the bottom or the basal level, just like DSI does on VSI-VFN synapse.

One good news can produce a transient increase in stock market, just like DSI does.
I call it "heteroeconomic facilitation."
The effects of a breaking news is bidirectional, sometimes biphasic, depending on the timing and state of the market.

Unlike synaptic strength though, the problem in market price is that we don't know where the bottom lies.

Reference: Sakurai and Katz (2009)

What I learned in Puerto Rico

- A Nautilus has 90 tentacles. (Jennifer Basil and R. Crook)
- The vertical lobe system of cephalopod brain resembles mammalian cortex. The axons of median superior frontal lobe neurons project to the small amacrine interneurons en passant. (Binyamin Hochner et al.)
- Oral veil has peripheral ganglia. They are bilaterally independent. Small 5-HT cells near MCC project there. (Rhanor Gillette)
- cAMP produces persistant Na current that plays a role in long-term memory in Lymnea. (George Kemenes)
- Ca-activated PKC activates AC in B51 in operant conditioning. (Jack Byrne)
- Intermediate-term potentiation involves postsynaptic Ca signal. (David Glanzman)
- Homosynaptic depression of Aplysia sensory-motor synapse is caused by decrease in the number of release sites and the reduction of release per varicosity. (Guy Malkinson and Micha Spira)
- Spontaneous transmitter release from the presynaptic neuron is both necessary and sufficient to recruit postsynaptic mechanisms of intermediate- and long-term synaptic plasticity in Aplysia. (Robert Hawkins)
- Injured axon produce afterdischarge in response to a train of stimuli. Some primitive plasticity signals in addition to Ca²⁺. (Edgar Walters)
- Bitter solution works very well for land slug learning. (Ryota Matsuo)
- Reversal of synapse from inhibitory to excitatory after formation of soma-to-soma synapse of Lymnaea neurons by appearance of nAChR. RTK inhibitor, Lavendustin A. (Fenglian Xu)
- Reversal of microtubules occurs when axon is transected. Awesome movies of microtubule formation and axonal transport. (Micha Spira)
- PKC-19-31 blocks homosynaptic depression. Burst-dependent protection of depression... Is this really preventing the depression or simply causing an overriding facilitation? (Tom Abrams)
- Translocation of PKC can be visualized. PKA downregulates PKC in Aplysia sensory neurons. (Wayne Sossin)
- Single action potential can terminate PTP. (Naweed Syed)
- In octopus, each sucker has its own ganglion. A sucker can pinch a string. Nice arm-sucker co-ordination. (Frank Grasso)
- Something mediates semi-sinchronous activity of left and right B67. (Mark Miller)
- The amplitude of EPSP evoked by B21 is determined not only by the degree of AP propagation, but also some nifedipine-sensitive Ca influx. (Betsy Cropper)
- There are five 5-HT cells in early laval state of molluscs. (Roger Croll)
- There is cut-end accumulation of FMRF-amide. (Ferdinand Vilim)
- Delayed rectifier type K channels form clusters near soma. PKC activation recruites Ca channels to the membrane at the terminals. (Leonard Kaczmarek)
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Molluscan neuroscience meeting

I am attending the molluscan neuroscience meeting in Old San Juan, Puerto Rico.

This meeting can be one of the best meetings I ever attended.
So many good talks. Many big-name people. Beautiful data and movies by highly advanced techniques.
It is great to meet some of my SfN friends again. Especially on a dispatched island in Caribbean ocean.
This whole meeting is like a field trip.

The open discussion made by Drs. Hawkins, Glanzman, Abrams and Byrne and others was terrific. I had never seen anything like that, although the topic they were discussing over and over did not sound that much important to me.

Having a field trip to the beach was also good. Seeing those smart people wearing WalMart-like bathing suits is kinda rare experience.

Only thing I regret to death was that I forgot to credit Drs. Russell Wyeth and Owen Woodward for their beautiful Tritonia swimming movie I used in my talk. Russel has many good Tritonia movies.

http://people.stfx.ca/rwyeth/vidsimages.html

Giving a talk

I gave a talk yesterday. I think it went very well. Paul seemed happy with it. I received many good comments.

I am usually not good at giving a speech. I often get choked even when I present my data in our weekly lab meeting. This is not because of English. I am not good at giving a speech even in Japanese.

However, sometimes I feel very comfortable standing on a big stage. This happened yesterday. I didn't want to finish my talk. I felt like to talk about my stuff forever. I don't know why. I even remember that a mosquito was flying in front of the screen. I kinda enjoyed watching it while talking about heterosynaptic plasticity. I wish this happens every time I give a talk.