Ion channel distributions in cortical neurons are optimized for energy-efficient active dendritic computations

The mammalian brain uses more than 20% of the energy consumed by the entire body. This enormous demand for energy is thought to impose strong selective pressure by which neurons evolve in ways that ensure robust function at minimal energy cost. Here we demonstrate that the ion channel expression patterns by which pyramidal tract neurons - the major output cell type of the cerebral cortex - could implement their complex intrinsic physiology is extremely widespread. Surprisingly, this wide spectrum does not reflect morphological variability, but the energy costs for generating dendritic calcium action potentials. We found that energy-efficient calcium action potentials require a low expression of slow inactivating potassium channels in the distal dendrites, an empirical observation whose significance remained unclear for more than a decade. Thus, cortical neurons do not utilize all theoretically possible ways to implement their functions, but instead appear to select those optimized for energy-efficient active dendritic computations.

Calcium waves

Waves through living systems are best characterized by their speeds at 20°C. These speeds vary from those of calcium action potentials to those of ultraslow ones which move at 1–10 and/or 10–20 nm s −1 . All such waves are known or inferred to be calcium waves. The two classes of calcium waves which include ones with important morphogenetic effects are slow waves that move at 0.2–2 μm s −1 and ultraslow ones. Both may be propagated by cycles in which the entry of calcium through the plasma membrane induces subsurface contraction. This contraction opens nearby stretch-sensitive calcium channels. Calcium entry through these channels propagates the calcium wave. Many slow waves are seen as waves of indentation. Some are considered to act via cellular peristalsis; for example, those which seem to drive the germ plasm to the vegetal pole of the Xenopus egg. Other good examples of morphogenetic slow waves are ones through fertilizing maize eggs, through developing barnacle eggs and through axolotl embryos during neural induction. Good examples of ultraslow morphogenetic waves are ones during inversion in developing Volvox embryos and across developing Drosophila eye discs. Morphogenetic waves may be best pursued by imaging their calcium with aequorins.

Hyperpolarization-Activated Current Ih Disconnects Somatic and Dendritic Spike Initiation Zones in Layer V Pyramidal Neurons

Layer V pyramidal cells of the somatosensory cortex operate with two spike initiation zones. Subthreshold depolarizations are strongly attenuated along the apical dendrite linking the somatic and distal dendritic spike initiation zones. Sodium action potentials, on the other hand, are actively back-propagating from the axon hillock into the apical tuft. There they can interact with local excitatory input leading to the generation of calcium action potentials. We investigated if and how back-propagating sodium action potentials alone, without concomitant excitatory dendritic input, can initiate calcium action potentials in the distal dendrite. In acute slices of the rat somatosensory cortex, layer V pyramidal cells were studied under current-clamp with simultaneous recordings from the soma and the apical dendrite. A train of four somatic action potentials had to reach high frequencies to induce calcium action potentials in the dendrite (“critical frequency,” CF ∼100 Hz). Depolarization in the dendrite reduced the CF, while hyperpolarization increased it. The CF depended on the presence of the hyperpolarization-activated current Ih: blockade with 20 μM 4-( N-ethyl- N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288) reduced the CF to 68% of control. If the neurons were stimulated with noisy current injections, leading to in-vivo-like irregular spiking, no calcium action potentials were induced in the dendrite. However, after Ih channel blockade, calcium action potentials were frequently seen. These data suggest that Ih prevents initiation of the dendritic calcium action potential by proximal input alone. Dendritic calcium action potentials may therefore represent a unique signature for coincident somatic and dendritic activation.

Ca2+-Activated Nonselective Cationic Current (I CAN) in Turtle Motoneurons

The presence of a calcium-activated nonspecific cationic (CAN) current in turtle motoneurons and its involvement in plateau potentials, bistability, and windup was investigated by intracellular recordings in a spinal cord slice preparation. In the presence of tetraethylammonium (TEA) and tetrodotoxin (TTX), calcium action potentials evoked by depolarizing current pulses were always followed by an afterdepolarization associated with a decrease in input resistance. The presence of the afterdepolarization depended on the calcium spike and not on membrane potential. Replacement of extracellular sodium by choline or N-methyl-d-glucamine (NMDG) reduced the afterdepolarization, confirming that it was mediated by a CAN current. Plateau potentials and windup were evoked in response to intracellular current pulses in the presence of agonist for different metabotropic receptors. Replacement of extracellular sodium by choline or NMDG did not abolish the generation of plateau potentials, bistability, or windup, showing that Na+ was not the principal charge carrier. It is concluded that plateau potentials, bistability and windup in turtle motoneurons do not depend on a CAN current even though its presence can be detected.

Calcium action potentials in retinal bipolar neurons

Patch-clamp and calcium-indicator measurements were used to examine the electrical excitability of large-terminal bipolar neurons from goldfish retina. Large, transient increases in intracellular calcium occurred spontaneously in the synaptic terminal but not in the soma of bipolar neurons. Calcium transients were blocked by hyperpolarization, by external application of calcium-channel blockers, and by the neurotransmitters GABA and glutamate. These observations suggest that calcium action potentials are responsible for the spontaneous increases in intraterminal calcium, which was directly confirmed by electrical recordings of calcium-dependent action potentials in both whole-cell and perforated-patch recordings. We suggest that regenerative depolarization produced by the opening of calcium channels in the synaptic terminal of on-type bipolar neurons represents an amplification mechanism in the high-sensitivity ON pathway in the dark-adapted fish retina.