Sunday, July 4, 2010

Forum European Neuroscience

Hey all,

It's been too long since I posted here. The main reason being the preparation for FENS (Forum of European Neuroscience). Today is the second day of the conference and the debate on a few things is clearly on:
* Is there rebound in CN neurons under invivo awake conditions?
* If there is rebound in CN neurons, what would it do?
* Up- and downstates in the cerebellum, are they real, or an artifact? (Yes, I hear you! Not again!!!!!!)
* Up- and downstates in the cerebrum: an effect of anesthesia and sleep?

So, expect me to post a few things about these subjects the coming time. I think these questions will keep me occupied for a while.

Thursday, May 13, 2010

Understanding Animal Research

It's been a while since I posted something here. I found a very good website with balanced views on animal research: Understanding Animal Research. And they're on facebook as well! Unfortunately we don't have anything like this in The Netherlands.

Wednesday, February 24, 2010

Animal rights terrorists

The reason I only call myself 'Neuronerd' is simple. I don't want my appartment to be set on fire, or my family harassed.
The situation is outrageous!
Terrorist website (Warning caps-lock key is stuck on this blogger's keyboard)
It's time to get mad I agree, we should not let these nutcases win.

Brain development

Here's an awesome cartoon from Jorge Cham, artist behind "PhD Comics". Check out his website: Piled Higher and Deeper
(WARNING!!! Procrastination awaits you!)

Monday, February 8, 2010

Patching in awake animals gets you into Science!

Navigation activates the hippocampus. For each location we visit, specific place cells are activated. Conventionally, place cells are recorded by using chronic single- or multi unit recordings. The biggest drawback of these techniques is the lack of information about what is happening inside the cell. This part of information has been lacking for a long time. Whole cell, or sharp electrode recordings can provide this information, but are very challenging in awake behaving animals. The group of Michael Brecht (who else) have taken the challenge and recorded from a number of hippocampal neurons in awake navigating animals (Epsztein et al. Science, 2010).

The most interesting finding is the occurence of spikelets in these neurons. These spikelets are different from spikes and EPSPs, but still they are correlated with navigation. Of course this all sounds very interesting, but is it actually? What are we learning here? The spikelets probably do not transmit down the axon because they reflect subthreshold activity. They can, like EPSPs, be underlying spikes in these neurons. But, these spikes could have been detected by extracellular means as well.

Then there must be some exciting story at the input site! Of course there must be a cool story here, otherwise 'Science' would never consider it for publishing. Unfortunately, the authors have no clue what they are looking at. They propose axo-axonal coupling, dendritic spikes or extopic axonal spikes. But none of these explanations have been tested here. So, the input side of this story has not been investigated properly yet.

Now, what did we learn from this? 1. There are spikelets in hippocampal principal cells. 2. These spikelets can be underlying spike firing. 3. spikelets are correlated with navigation in a similar way as spikes.
So it seems that using a fancy technique is enough to get into science. Let's all go for patching in free-flying zebra finches. Not because we might actually learn something from it, but because we can and it gets us into 'Science'.

Monday, January 11, 2010

fMRI - A Validated Method?

Already in 2001 research cast substantial doubt on the underlying mechanism for the generation of a BOLD response in fMRI. Logothetis and collegues (Logothetis et al. Nature 2001) found that the BOLD response more accurately reflected synaptic input into an area than the actual spike output from the area. Viswanathan and Freeman took this argument further and showed that there didn’t need to be spikes to generate a BOLD response (Viswanathan and Freeman Nature Neuroscience, 2007). But this poses a problem. According to the Hodgkin-Huxley model of spike generation there is a substantial energy demand for each spike.

Now this apparent discrepancy has been resolved by Henrik Alle and colleagues (Alle et al. Science, 2009). In hippocampal mossy fibers they have found that the overlap in sodium and potassium flux is minimally overlapping. This enables the axons to generate action potentials with only 1.3 times the theoretical minimum energy (charging a perfect capacitor). This stands in stark contrast to the previously estimated 4.0 times the theoretical minimum.

The researchers came to this conclusion by applying previously recorded action potential waveforms as a voltage command to outside-out patches. The recorded sodium and potassium ion-fluxes were isolated and recorded. Interestingly, the percentage of overlap between the two ion-fluxes was as low as 20% of the total charge. Additionally, it seems that the calcium influx at the presynaptic membrane costs approximately 6 times as much as a spike traveling down the axon. This stresses the relative high energy consumption of synaptic transmission as opposed to action potential firing.

Carter and Bean (Carter and Bean Neuron, 2009) took these observations even further and investigated action potential energy consumption across several neuron types. Fast spiking neurons, like GABA-ergic interneurons, have much narrower spikes than slower spiking neurons, like neocortical pyramidal cells. They found that fast spiking comes at a cost. For narrower action potentials the sodium and potassium need to overlap; and consequently, the energy consumption per action potential for these fast spiking neurons is considerably higher than the 1.3 times the theoretical minimum Alle and collegues found.

Taken together it seems that the energy consumption per action potential, even for fast spiking neurons, is considerably smaller than previously assumed. This has implications for the interpretation of fMRI data. Action potential firing is probably not the underlying neuronal mechanism for the fMRI BOLD response. Most likely, the BOLD response is caused by synaptic communication. Thus projections to a brain area might be contributing to the BOLD response just as much as processing in that brain area.

Neuro Nerd