Neurons communicate with each other via release of neurotransmitters. Since neurotransmitter release is largely driven by the discharge of an action potential, we can use the frequency at which a neuron generates action potentials as a measure of its "communicative" ability. Counter-intuitively, some types of neurons "resist" generating action potentials in response to elevated excitatory neurotransmission, a phenomenon known as "Depolarization Block." The current video is an extracellular recording of a midbrain dopaminergic neuron, which begins entering into Depolarization Block at the 40s mark, in response to intense glutamatergic receptor activation (via an NMDA agonist). Note that the video is divided vertically into two major components: (LEFT HALF) action potential frequency during a period of increasing stimulation; (RIGHT HALF) extracellular recordings of action potential voltage during 5ms "sampling windows." On the RIGHT HALF of the video, each "flicker" of the up-down signal represents the occurrence of an action potential. As the video time elapses, you will notice that the computer generates a sound as a function of signal's maximum voltage: higher voltages generate "shrill" clicks, while lower voltages generate "throaty, gritty" clicks. On the LEFT HALF of the video, you see a chart whereby the x-axis is elapsed time (in seconds), while the y-axis includes nominal rows of one-dimensional data. As the recording progresses, you will notice an x-axis cursor moving across all three rows. The nominal rows on the LEFT HALF of the video correspond with: 1. Dosage Label, top row. The "Keyboard" text, followed by "1 - 0" indicates that the number "10" was entered into the computer's keyboard during the recording, signifying that 10 nA of NMDA -- a glutamate receptor agonist -- is the dosage" for the Stimulation Period (next row). 2. Stimulation Period Onset/Offset, middle row. The "NMDA 20" text tells us that, during the stimulation period (contained in the rectangle), 20mM of NMDA is being ejected at a constant rate of 10 nA. 3. Action Potential Frequency, bottom row. Each vertical line represents the point in time in which the rising phase of a recorded action potential crosses the signal-to-noise threshold for the recording (here, set at 0.05 volts). The "Activity" row is the real "meat and potatoes" of the collected data: lines clustering in close proximity demonstrate periods of elevated action potential generation, while areas of "white space" demonstrate periods of inhibited action potential generation. So, what's happening here? During the stimulation period, NMDA builds-up in the dopamine neuron's extracellular/synaptic space, prompting the neuron to generate action potentials at an escalating rate (0:02 - 0:40). NMDA binds to more and more subsites on somatodendritic glutamate receptors, spreading from a small space near the recording probe to a larger space as the volume diffuses. For unclear reasons that are still being investigated, there appears to be a maximum rate at which a dopamine neuron can generate action potentials in response to excitatory neurotransmission: once this rate is met or exceeded, action potential production sharply decreases (0:40 - 1:04). The moment we shut-off NMDA ejection (1:04), you see that the neuron quickly reverts to its baseline firing rate, as the drug quickly diffuses out of the extracellular space and/or is released from binding sites.

• published: 14 Nov 2013
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