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Sound localization and timing computations in the auditory brain stem. J Rinzel, NYU

Computational and experimental study – coincidence detection and ITD coding (gerbil MSO, in vitro) Subthreshold dynamic negative feedback: G KLT activ’n; phasic firing; brief temporal integration window; integration of noisy inputs (STA)

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Sound localization and timing computations in the auditory brain stem. J Rinzel, NYU

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  1. Computational and experimental study – coincidence detection and ITD coding (gerbil MSO, in vitro) • Subthreshold dynamic negative feedback: GKLT activ’n; phasic firing; brief temporal integration window; integration of noisy inputs (STA) • The definitive feedforword neuron: bipolar dendrites and distrib’n of Iion • Coding: • population coding (slope or place code?); role of inhibition; role of EPSP asymmetries + IKLT; • stimulus dependent filter/selectivity. with G Svirskis, R Dodla, V Kotak, D Sanes, M Day, B Doiron, P Jercog, N Golding Funded by NIMH, NIDCD and NSF. Sound localization and timing computations in the auditory brain stem. J Rinzel, NYU

  2. In vivo data from the barn owl shows NL neurons encode ITD ITD sensitivity arises from a coincidence detection mechanism, as in the Jeffress model % MAXIMUM RESPONSE 100 4409 Hz -30 µsec 5 50 A B DELAY LINE INPUTS 0 -150 150 300 C 0 -300 C left ear leads right ear leads DELAY LINE INPUTS INTERAURAL TIME DIFFERENCE (µsec) D E PLACE CODE OUTPUTS

  3. … place code or slope code? • in vivo gerbil: ITD-tuning peak is outside physiol range. • Inhibition shapes ITD-tuning. Brand et al. Nature, 2002

  4. MSO neurons fire phasically, not to slow inputs. Blocking I KLT may convert to tonic. J Neurosci, 2002 Even after reducing I KLT, some neurons (older) remained phasic. INa fairly inactivated near rest.

  5. IKHT IKLT Idealized model: integrate and fire with “IKLT” INa Network, 2003. mV mV msec HH-type model with currents: INa IKHT and subthreshold IKLT J Neurosci, 2002 Phasic firing properties

  6. Slow ramp: no spike Fast ramp: one spike

  7. Schematic of circuit for low frequency coincidence detection in mammals. (D Sanes w/ focus on gerbil.)

  8. Network, 2003. Spike-generating current by reverse correlation. I, nA leaky I&F + IKLT 0.2 leaky I&F leaky I&F + IKLT below RMP 0.1 0.0 -8 -6 -4 -2 0 time before spike, ms Poisson PSGs from Nex + Ninh input fibers spont rate Some expts: Detection of subthreshold signal amidst noisy background IKLT narrows temporal integration window. Notice “dip”: IKLT is partially active at rest; transient hyperpolarization promotes spiking by deactivating IKLT.

  9. J Neurosci, 2002 Response of MSO cell to brief “signal” in noise. Control After DTX DTX (IKLT blocker) ==> -- widening of integration window -- reduction of “dip” Poisson PSGs from Nex + Ninh input fibers Spike triggered average “Isyn”, expeimental

  10. Selectivity endowed by IKLT depends on spectral profile of the input. w/ Day, Doiron J Neurophys, 2008. Stim selec’n diff’ce (SSD)= 1-misclassification error 150 Hz 650 Hz • Rothman-Manis (HH-type) 2003 model: Dynamic vs Frozen IKLT • Noisy input I(t); STEs {IST(tj)} discrete time ti 2 clouds in vector space • Discriminant analysis (feature extraction) finds “direction” • that maximizes “distance” between clouds (Fisher criterion)  projections of {IST(tj)} • For white noise input: no difference in STAs.

  11. Reduction of “false positives” Coincidence detection – a role for dendrites Compartmental model; 2-variable minimal phasic model Gradient of length along tonotopic axis. Agmon-Snir, Carr, Rinzel: Nature ‘98

  12. gex(t), τex=0.2 ms gKLT in S, IS and weak in D; active or “frozen” (passive); gNa only in Axon. spike generation Biophysical model: gerbil MSO -- dendrites w/ P Jercog and Golding lab … ongoing “HH-type” cable model, based on I,V-clamp data (in vitro, gerbil, Golding, 2006). l/λ≈ 0.6-0.8 τm ≈ 0.6-1 ms

  13. EPSP attenuation and temporal sharpening - subthreshold Experiment Golding lab Theory Jercog, Rinzel + V-clamp If gKLT is “frozen”.

  14. Attenuation and sharpening grow with propagation distance in model. Experiment Theory

  15. Time difference sensitivity, enhanced for inputs to dendrite – subthreshold case.

  16. “direction selectivity” Motion direction sensitivity. Passive cable, Rall (1964). Proximal to distal sequence: rapid rise, broad EPSP at soma. Distal to proximal sequence: latency, buildup to higher peak EPSP.

  17. Response to “near then far” input is disadvantaged by wake of (dendritic) gKLT along path to Soma.

  18. Synaptic input must be fast for spike generation. Include axonal spike generation τex=0.2 … spike τex=0.5 no spike

  19. Coincidence detection in model… with spikes in axon the definitive feedforward neuron. “ITD” = 0.1 ms “ITD” = 0.15 ms No back-propagating action potential.

  20. Contralateral excitation is preceded by inhibition. • Ipsilateral excitation precedes inhibition. Tuning for Interaural Time Difference (ITD), shaped by transient inhibition • ITD peak is outside physiol range • Blocking inhibition shifts the ITD-tuning curve to “0”. in vivo, gerbil Brand et al, 2002 Place code or slope code? Grothe, New roles for synaptic inhibition in sound localization, Nat. Rev. (2003)

  21. ITD ipsi contra Δ ITD tuning in small mammals is sensitive to timed inhibition  slope code Brand et al, Nature, 2002 Results with MSO cell model. Rothman et al ’93 Key parameters: τinh= 0.1 ms, Δ = 0.2 ms

  22. Asymmetry in EPSPs shapes ITD tuning w/ Jercog, Sanes, Svirksis, Kotak - ongoing Contra EPSPs slower than Ipsi EPSPs Ipsi leading Contra leading If contra-EPSP is slower-rising, itrecruits more IKLT before fast rise to threshold – lowering probability to fire. In vitro thick slice ITD in dish.

  23. Asymmetry in EPSPs shapes ITD tuning w/ Jercog, Sanes, Svirksis, Kotak - ongoing In vitro thick slice ITD in dish. Contra pathway is longer  greater latency for EPSPs Contra inputs are slower rising.

  24. Effect of inhibition -- counteracts the advantage of faster-rising ipsi inputs... With inhibition Inhibition blocked τinh = 2 ms

  25. Computational and experimental study – coincidence detection and ITD coding (gerbil MSO, in vitro) • Subthreshold dynamic negative feedback: GKLT activ’n; phasic firing; brief temporal integration window; integration of noisy inputs (STA) • The definitive feedforword neuron: bipolar dendrites and distrib’n of Iion • Coding: • population coding (slope or place code?); role of inhibition; role of EPSP asymmetries + IKLT; • stimulus dependent filter/selectivity. with G Svirskis, R Dodla, V Kotak, D Sanes, M Day, B Doiron, P Jercog, N Golding Funded by NIMH, NIDCD and NSF. Sound localization and timing computations in the auditory brain stem. J Rinzel, NYU

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