Release probability increases towards distal dendrites boosting high-frequency signal transfer in the rodent hippocampus

  1. Dmitri A Rusakov  Is a corresponding author
  2. Thomas P Jensen  Is a corresponding author
  3. Olga Kopach
  4. James P Reynolds
  5. Leonid P Savtchenko
  1. Queen Square UCL Institute of Neurology, University College London, United Kingdom
6 figures, 1 table and 1 additional file

Figures

Figure 1 with 1 supplement
Optical quantal analysis at individual CA3-CA1 synapses reports higher release probability towards distant dendrites.

(A) CA1 pyramidal cell held in whole-cell mode (acute hippocampal slice), dialysed with 50 µM AF 594 and 300 µM Fluo-8 (75 µm z-stack average, λx2p = 800 nm; AF 594 channel). Dotted rectangles (S1 …

Figure 1—figure supplement 1
Optical quantal analysis at individual CA3-CA1 synapses in acute hippocampal slices: second-order dendrite.

(A) CA1 pyramidal cell held in whole-cell mode dialysed with 50 µM AF 594 and 400 µM OGB-1 (75 µm z-stack average, λx2p = 800 nm; DIC + AF 594 channel combined). Patch pipette (patch) and …

Figure 2 with 1 supplement
Selected features of excitatory synapses with respect to their dendritic location.

(A) Average release probability (Pr) at individual synapses plotted against distance to the first dendrite branching point. Solid line, linear regression (p value to reject H0 = zero slope and …

Figure 2—figure supplement 1
Selected features of excitatory synapses with respect to their dendritic location.

(A) Average probability of the second release (paired-pulse stimuli 50 ms apart) plotted against distance to the soma; sample mean ± SEM: 0.633 ± 0.20 (n = 41). (B) Paired-pulse ratio (as P2/P1 in C)…

Figure 3 with 1 supplement
Evoked glutamate release from Schaffer collaterals shows lower paired-pulse ratios at greater distances from pyramidal cell bodies.

(A) Experimental design: area of the hippocampal slice with iGluSnFR expressed in neuronal membranes (green channel); arrow, measured distance d between CA1 pyramidal cell body layer and the axonal …

Figure 3—figure supplement 1
Optical (multi-synaptic) glutamate signal evoked by short bursts of Schaffer collateral stimulation at varied distances from s.pyramidale.

(A) Examples of recorded ROIs (iGluSnFR green fluorescence channel, dotted ovals) in s. radiatum, with groups of stimulation-responding tentative axonal boutons expressing iGluSnFR, at different …

Figure 4 with 1 supplement
Computer simulations of CA1 pyramidal cell with stochastic excitatory synapses.

(A) Diagram, NEURON model of a reconstructed CA1 pyramidal cell (Migliore et al., 1999) (ModelDB 2796; variable time step dt, t = 34°C). 50 excitatory inputs (blue dots) generate bi-exponential …

Figure 4—figure supplement 1
Simulating the experiment-based kinetics of short-term plasticity (STP) in the CA3-CA1 circuit.

(A) Traces show simulated average somatic response to five-burst 20 Hz stimuli (NEURON model as in Figure 4A), with synaptic Pr values distributed either uniformly randomly (black line), or in …

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Tables

Key resources table
Reagent type (species) or resourceDesignationSource or referenceIdentifiersAdditional information
Chemical compound, drugPicrotoxinTocrisCat. # 1128
Chemical compound, drugD-SerineSigma AldrichCat. # S4250
Chemical compound, drugOregon Green 488 BAPTA-1, Hexapotassium SaltThermoFisherCat. #O6806
Chemical compound, drugAlexa Fluor-594 HydrazideThermoFisher ScientificCat.# A10438
Chemical compound, drugFluo-8, potassium saltStratech ScientificCat.# 21087-AATOriginal Source: (Teflabs)
No longer exists
Chemical compound, drugFluo-4, Pentapotassium SaltThermoFisher ScientificCat.# F14200
Chemical compound, drugAgaroseSigma-AldrichCat. #9539; CAS: 9012-36-6Freshly prepared (4%)
Chemical compound, drugD-glucoseSigma-AldrichCat. #G8270; CAS: 50-99-7Freshly prepared (10 mM)
Chemical compound, drugKClSigma-AldrichCat. #P9333; CAS: 7447-40-7
Recombinant DNA reagentAAV9.hSynap.iGluSnFr.WPRE.SV40Penn Vector CoreAddgene
Cat. # 98929-AAV9
Strain, strain background
(Sprague-Dawley rat)
Sprague-DawleyCharles River UKCrl: CD (SD)
Strain: 0204
Strain, strain background
(C57BL/6J mouse)
C57BL/6JCharles River UKC57BL/6NCrl
Strain: 0159
Software, algorithmImageJNIHRRID:SCR_003070
https://imagej.nih.gov/ij/
Software, algorithmpClamp10Molecular DevicesRRID:SCR_011323
https://www.moleculardevices.com/products/axon-patch-clamp-system/acquisition-and-analysis-software/pclamp-software-suite
Software, algorithmOriginProOriginLab IncRRID:SCR_014212
https://www.originlab.com/origin
Software, algorithmMES 4.x-5.xFemtonics Ltd.RRID:SCR_018309
https://uk.mathworks.com/products/connections/product_detail/femtonics-mes.html
Software, algorithmWinWCP Versions 4.x-5.xStrathclyde Electrophysiology SoftwareRRID:SCR_014270 http://spider.science.strath.ac.uk/sipbs/software_ses.htm
Software, algorithmMatlabMathworksRRID:SCR_001622 https://uk.mathworks.com/products/matlab.html
Software, algorithmNEURON 7.6 × 64https://www.neuron.yale.edu/neuron/RRID:SCR_005393
Software, algorithmKinetics of CA1 pyramidal neuronhttps://senselab.med.yale.edu/ModelDB/ShowModel?model=2796#tabs-2RRID:SCR_005393
model = 2796#tabs-2
Software, algorithmreconstructed CA1 pyramidal neuronshttps://senselab.med.yale.edu/ModelDB/ShowModel?model=7509#tabs-1RRID:SCR_005393
model = 7509#tabs-1
OtherMulticlamp 700BMolecular DevicesRRID:SCR_018455
OtherOlympus FluoView1000OlympusRRID:SCR_014215
OtherFemto3D RCFemtonicsFemto3D RC
OtherBioRad Radiance 2100BioRadRadiance 2100
OtherLeica VT1200S vibratomeLeica BiosystemsRRID:SCR_018453

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