The beat goes on: spontaneous firing in mammalian neuronal microcircuits.
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Action Potentials↗
Biomedical subjects
Spencer L Smith
Publications and source records attributed to Spencer L Smith.
An ultra small array of electrodes for stimulating multiple inputs into a single neuron.
We have developed an ultra small, translucent array of electrodes for use in the parasaggital cerebellar slice preparation. This positionable array is capable of stimulating multiple independent bundles of parallel fibers (PFs), which synapse onto a single Purkinje neuron. On a silicon substrate, a low-stress silicon nitride film was used both as a structural layer and as electrical insulation. Evaporated gold pads and interconnects were sandwiched between two such layers. A bulk anisotropic silicon etch released the individual arrays. The electrodes are supported within a 2-microm-thick cantilever of translucent silicon nitride. In one design, eight 4-microm-wide square electrodes are arranged on 8-microm-centers. Another design, half the scale of the first, was also tested. The array was mounted on a micromanipulator and can be visualized by an upright microscope. It can then be positioned in the dendritic arbor of a Purkinje neuron while not disturbing a recording pipette at the soma. Paired-pulse facilitation experiments have confirmed that the electrodes are capable of stimulating non-overlapping bundles of PFs. This device will be useful for exploring spatiotemporal synaptic integration in single neurons. Potential applications in experiments on cerebellar LTD are also discussed.
Animals↗
Persistent changes in spontaneous firing of Purkinje neurons triggered by the nitric oxide signaling cascade.
Many types of neurons fire spontaneously because of the activity of pacemaking ion channels. Although endogenous firing can serve as a persistent signal to downstream targets, little attention has been paid to factors that might modulate such intrinsic electrical activity. We tested for modulation of spontaneous firing of Purkinje neurons in cerebellar slices under conditions in which principal synaptic inputs were blocked. Loose-patch recordings from single neurons show that sustained (>40 min) increases in the spontaneous firing rate can be triggered by activation of the nitric oxide-cGMP signaling pathway. Inhibitors of soluble guanylate cyclase and protein kinase G block this modulation. Increases in firing rate are also observed after stimulation of parallel fibers but not in response to basket cell activity. These findings elucidate a novel role for the nitric oxide-cGMP signaling cascade in the brain. This mechanism could permit long-term adjustments in the baseline firing rate of endogenously active neurons in response to changes in afferent activity.
Action Potentials↗