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Whatdoesthisdatafigureshow? Beattyetal.,J.Neurophysiol., 2015 Wehavediscussedmultiplephysiologicalpropertiesthatcaninfluence neuralresonance.Howeasydoyouthinkitisforaneurontochangeits resonantfrequency? Isthissomethingthatcouldhappennaturally? Atwhattimescale? Magnitude ofImpedance Modelsofneuronsaselectricalcircuitstounderstandresonance (due topassiveproperties) (due toactivecurrents) Inputimpedance =determineshowmuchaneuron depolarizes inresponse toanalternatingcurrent AdaptedfromHutcheon andYarom,TrendsinNeuroscience,2000 Toclarify(notonexam): 1.Asthemembrane“charges” tothenewvoltage,the charging currentapproaches zero. Whenanion channelopensorcurrentis injectedintothecell,voltagechanges occurslowlyacrossthemembrane.This changeisevenslowerinlargecellsor cellswithmanypassivechannelswhich “leak”current. 2.Currentflowacrosspassive channelsincreases V Voltageacrossthemembrane I Currentpulse Modelsofneuronsaselectricalcircuitstounderstandresonance Neuronsthatexhibitresonance have: PassiveChannel 1) Channelsthatallowthepassiveflowof ionsacrossthemembraneandenablethe suppression ofresponses toinputs that occurathigh frequencies. 2) Voltage-gatedion channelsthatoppose changestothemembranepotentialand suppress responsestoinputsthatoccurat lowfrequencies. Voltage-gatedChannel Modelsofneuronsaselectricalcircuitstounderstandresonance Theresonantfrequency,orpreferred frequency, canchangedepending upon physiological properties oftheneuron. Forexample: PassiveChannel 1) Thesizeoftheneuron influences the capacitance,suchthatlargerneurons respond slower(worse)tohighfrequencies. 2) Differentvoltage-gatedchannelscounteract changestothemembranepotentialina unique manner. Voltage-gatedChannel ThisisourFridayactivity! Modelsofneuronsaselectricalcircuitstounderstandresonance PassiveChannel Attherestingmembranepotential, voltage-gatedchannelsareclosed. Deviationsfromtherestingmembrane potentialcanactivatevoltage-gated channelsthatpromote resonance. Voltage-gatedChannel Resonance,dueto voltage-gatedNa+ channels Fast-spiking(FS) interneurons inthestriatum: Resting membrane potential Beattyetal.,J.Neurophysiol., 2015 Howdoweidentifythechannelsthatcauseresonance? VoltageClamp: 1 2 1.Thevoltageacrossthecellmembraneis measuredusing intracellularrecording techniques. 2.Involtage-clamp,acurrentisinjectedto maintainadesired voltage. 3.Itispossible tomeasurethecurrentthat isinjectedtoobtainacertainvoltage. 4.Theimpedance ofthecellcanbe calculatedusing thefollowing equation: !"#$%&'(! ) Impedance=,-..'/$(0* ) * Howdoweidentifythechannelsthatcauseresonance? Adecreaseincurrentamplitude indicatesresonance VoltageClamp: Adesiredvoltagethatisasweep from1-40Hz Beattyetal.,J.Neurophysiol., 2015 Beattyetal.,J.Neurophysiol., 2015 Howdoweidentifythechannelsthatcauseresonance? Cholinergic Interneurons intheStriatum VoltageClamp: Placechannel blockers(e.g.,TTX) intothebath Beattyetal.,J.Neurophysiol., 2015 Power(dB) Frequency (Hz) Thedorsomedial striatumexhibitsdeltaoscillations: 0.5seconds AdaptedfromDeCoteau etal.,JNeurophysiol, 2007 Howdoweidentifythechannelsthatcauseresonance? CurrentClamp: 2 1 1. Incurrentclamp,acurrentisfirst injectedintothecell. 2. Changestothevoltageacrossthe membranearemeasured. !"#$%&'(! ) Impedance=,-..'/$(0* ) * Howdoweidentifythechannelsthatcauseresonance? ZAPCurrent: CurrentClamp: 2 1 Thalamocortical Neurons: slightlyhyperpolarized ~86mV AdaptedfromPuil etal.,Journal ofNeurophysiology, 1994 Thethalamusexhibitsdeltaoscillationsduring sleep: hyperpolarizedneuronsspikeataclocklikedeltaduetohyperpolarizationactivatedcation current(Ih): Baletal.,J.Neurophys.,1995 McCormickandBal,Ann.Rev.Neurosci.,1997 Wehavediscussedmultiplephysiologicalpropertiesthatcaninfluence neuralresonance.Howeasydoyouthinkitisforaneurontochangeits resonantfrequency?