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Published on: February 10, 2011
Hyperpolarization-activated currents in presynaptic terminals of mouse cerebellar basket cells
A P Southan1, N P Morris, G J Stephens
1Neuronal Excitability Group, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2BZ, UK.
Insights
Researchers identified a hyperpolarization-activated current (I(h)) in mouse cerebellar inhibitory presynaptic terminals. This finding suggests I(h) as a potential target for neuromodulation in the cerebellum.
Area of Science:
- Neuroscience
- Cellular Electrophysiology
Background:
- The cerebellum plays a crucial role in motor control and coordination.
- Basket cells are inhibitory interneurons in the cerebellum that synapse onto Purkinje cells.
- Hyperpolarization-activated currents (I(h)) are known to influence neuronal excitability.
Purpose of the Study:
- To investigate the presence and properties of I(h) in cerebellar inhibitory presynaptic terminals.
- To determine the functional role of presynaptic I(h) in synaptic transmission.
- To identify potential molecular candidates for presynaptic I(h).
Main Methods:
- Patch-clamp recordings from mouse cerebellar basket cell terminals and somata.
- Pharmacological manipulation using cesium (Cs+) and ZD 7288 to block I(h).
- Analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) in Purkinje cells.
Main Results:
- A hyperpolarization-activated current (I(h)) was successfully recorded from cerebellar basket cell terminals.
- Presynaptic I(h) exhibited rapid activation and deactivation kinetics, sensitive to Cs+ and ZD 7288.
- Inhibition of I(h) significantly reduced the frequency and amplitude of spontaneous IPSCs in Purkinje cells.
- Similar I(h) properties were observed in basket cell somata, suggesting a widespread presence.
Conclusions:
- This study reports, for the first time, the presence of I(h) in mammalian inhibitory presynaptic terminals.
- Presynaptic I(h) in basket cells influences spontaneous neurotransmitter release onto Purkinje cells.
- I(h) represents a novel target for neuromodulation within the cerebellar circuitry.
- Specific hyperpolarization-activated cation channels are proposed as molecular candidates for this presynaptic I(h).
Abstract:
Using patch-clamp techniques, a hyperpolarization-activated current (I(h)) was recorded from synaptic terminals of mouse cerebellar basket cells. Ih was blocked quickly and reversibly by 2 mM Cs(+), and subtraction revealed a rapidly activating and deactivating I(h) current. Similar gating and block of presynaptic I(h) were also seen with the more selective inhibitor ZD 7288 (10 microM). The time constant of activation (tau (a))of presynaptic I(h) current became faster with membrane hyperpolarization, being approximately 74 ms at -130 mV, changing e-fold for a 33 mV change in membrane potential. Whole-cell recordings from basket cell somata also revealed an I(h) current, which was similarly sensitive to block by ZD 7288. Inhibition of I(h) by 10 microM ZD 7288 reduced the frequency ( approximately 34 %) and amplitude ( approximately 26 %) of spontaneous IPSCs (sIPSCs) recorded in Purkinje cells, one of the principal synaptic targets of basket neurones. This is the first report of an I(h) current in mammalian inhibitory presynaptic terminals, which may be an important target for neuromodulation in the cerebellum. Comparing the biophysical properties and distribution of cloned hyperpolarization-activated cation channels, we also suggest a molecular candidate underlying I(h) at these synapses.
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