Lobsters, Axons, Telephones, and Extracellular Recordings – A look at how neuronal signals can be transmitted differently under certain pharmacological conditions.

Neuronal signals are normally transmitted from cell bodies, or somas, to terminals via extensions called axons. At these terminals, connections called synapses are made with other neurons whereby the signals are released via the aide of chemical messengers called neurotransmitters. Many still believe that axons are reliable conductors of these signals.

However, with several years’ worth of experiments, scientists have questioned the fidelity of axonal conduction. They’ve realized that axons do not work like telephones. While telephones and axons may both have buttons – at the terminals in axons – only telephones faithfully conduct signals. And only telephones ring aloud and send messages to voicemail…

In any case, neuronal signals, unlike telephone signals, can change along their paths. Moreover, the pre-synaptic neuron may communicate a different message from the one originally sent from the soma to the synapse with the post-synaptic cell.  Researchers at the lab I’ve been working at this summer, the Whitney Laboratory for Marine Bioscience, have focused on the role of neuromodulation in signal transmission along axons, particularly by the well-known neurotransmitter – dopamine.

Top Left, Homarus americanus. Bottom Left, Nervous system pinned down for recordings. Right, Recordings in vivo and in vitro.

Dissecting out the stomatogastric nervous system of the Homarus americanus, or Maine Lobster, Dirk Bucher, Aleksander Ballo, and colleagues have been able to take extracellular – and intracellular – recordings from axons. Using these recordings, they focus on how signal transmission differs under control and pharmacologically affected conditions.

Bucher and Ballo are some of the first researchers to directly show that neuromodulators affect activation properties of axonal voltage-gated ion channels – particularly looking at HCN channels. First off, these channels carry the hyperpolarization-activated inward current, which brings positive ions into the axon and initiates depolarization. Secondly, researchers including Ballo and Bucher suggest these channels influence neuronal communication by affecting the timing and efficacy of spikes and bursts. Further, they suggest the channels balance positive and negative currents to improve fidelity when there is repetitive spiking; this type of spiking can occur through many central pattern generators, such as those involved in rhythmic behaviors like walking, chewing, and swimming.

Spikes can also be initiated peripherally by dopamine administration. Ballo and Bucher offer that dopamine acts through D1-type receptors to increase cAMP which then works to modulate HCN channels.

Second messenger mechanism by which dopamine increases cAMP to influence HCN channels and corresponding currents

Often this series of events increases axonal conductance. When the current at these HCN channels is blocked, dopamine has no effect, suggesting also its importance in fidelity of axonal conduction.

Hopefully with more research into how signals can be altered after production at the soma, we can better understand how rhythmic behaviors are initiated, maintained, and restored.

Source: Dopamine Modulates I_H in a Motor Axon – Ballo, Bucher, et. al, The Journal of Neuroscience

Free will is a hackneyed topic. Science seems to be telling us that free will doesn’t exist because behavior is governed by the brain and the brain operates on physical rules of cause and effect. There is no such thing as uncaused cause, which free will requires. For some people this is an unbearable notion; these folks hang on to their perceived volition as evidence that they are in fact free to do as they choose, without being constrained by their biology. Others swallow what science has espoused long ago; of these folks, some tend to be pessimistic, thinking that their lack of free will means that everything is pointless and that the best thing they can do for themselves is to blur the line between their behind and a comfortable couch, until scientists discover the new species Homo sofus.

Still others take the absence of free will and choose to not cry over spilled milk. These people don’t allow determinism to lower their outlook on life. Rightly so.

If we grant that we live in a deterministic universe, where the rules of physics dictate that everything has a cause, then free will – defined as the ability to act without prior constraints – is obsolete. But what does determinism actually mean? Just what is the nature of neural processes that act in decision-making? If the brain works by physical rules, shouldn’t we be able to predict with 100% accuracy what effect a certain neural signal will have on subsequent signals?

This is noteworthy because neurotransmission seems to defy these concrete deterministic rules. The probability of neurotransmitter release, for example, is stochastic in nature; given a certain stimulation, it is impossible to predict whether a neuron will release neurotransmitter or not. Only after many experimental stimulations is it possible to find the probability of transmitter release.

The brain makes up for this unreliability with redundant connections, but the question remains whether the concept of stochastic processes may be scaled up to the level of decision-making in the brain. Also, it is not clear if the unpredictability is due to truly random outcomes or some hidden variables that current scientific techniques cannot measure.

This means that not only is the will not free, but that it may also be determined by random events (possibly at the quantum level). One’s actions then are based on genetic makeup, environment and perhaps randomness. I’m afraid this will feed the pessimists’ appetites, but that’s inevitable with every scientific explanation of human nature.