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University of São Paulo

CÉSAR CEBALLOS PhD student

Supervisor

DR. PROF. ANTÔNIO CARLOS ROQUE Department of Physics

DR. PROF. RICARDO LEÃO Department of Physiology

SUBTHRESHOLD ACTIVE CONDUCTANCES SHAPE THE EPSPS IN CORTICAL

NEURONS

EPSPs

http://www.synsys.eu/general-public Purves et al. 2001

Subthreshold passive properties

Sterratt et al. 2011, Purves et al. 2001

𝑅𝑖𝑛 = 𝑑𝑉

𝑑𝐼

V(t) =I

gL,k

k

å1- e-t t( ) +V0,V(t) =

I

gL,k

k

å1- e-t t( ) +V0,

𝑉 𝑡 = 𝐼 ∗ 𝑅𝑖𝑛 ∗ 1 − 𝑒−𝑡

𝜏 + 𝑉0

𝜏 = 𝑅𝑖𝑛 ∗ 𝐶

Subthreshold active properties V(t) =

I

gL,k

k

å1- e-t t( ) +V0,V(t) =

I

gL,k

k

å1- e-t t( ) +V0,

What about the subthreshold active conductances ?

𝐼𝐿𝑒𝑎𝑘 = 𝑔𝐿𝑒𝑎𝑘 ∗ (𝑉 − 𝐸𝑟𝑒𝑣)

𝐼𝑎𝑐𝑡𝑖𝑣𝑒 = 𝑔𝑎𝑐𝑡 ∗ 𝐴(𝑉) ∗ (𝑉 − 𝐸𝑟𝑒𝑣)

𝑑𝐼𝐿𝑒𝑎𝑘𝑑𝑉

= 𝑔𝐿𝑒𝑎𝑘 Non voltage-dependent

𝑑𝐼𝑎𝑐𝑡𝑑𝑉

= 𝑔𝑎𝑐𝑡 ∗𝑑𝐴(𝑉)

𝑑𝑉

Voltage-dependent

Whe need new equations that take into account the active currents ¡¡

Activation variable

4950 5000 5050 5100 5150 5200-1

0

1

2

3

4

5

6

7

8

mV

-67

-77

-82

-87

-92

-97

Branco et al. 2016

Persistent sodium current amplifies the EPSPs

Intrinsic properties shape the EPSPs

Computational simulations of voltage dependence of Rin and τm.

Patch-clamp Patch clamp recording

CA1 pyramidal cell Whole cell patch

clamp

Jaffe & Brown. Journal of Neurophys 1997

Dynamic clamp

𝐼 = 𝑔𝑛𝑎𝑝𝑚𝑎𝑥 ∗ 𝐴𝑛𝑎𝑝 ∗ (𝑉 − 𝐸𝑁𝑎)

𝑑𝐴𝑛𝑎𝑝𝑑𝑡

= 𝐴𝑛𝑎𝑝

∞ − 𝐴𝑛𝑎𝑝𝜏

𝐴𝑛𝑎𝑝∞ =

1

1 + 𝑒(𝑉𝑚+50)/−6

Experimental results - INaP amplifies the EPSPs

http://www.life.umd.edu/grad/mlfsc/zctsim/ionchannel.html

Puffer fish

Rin and τ are voltage dependent

The persistent sodium current increases the input resistance and membrane time constant which amplifies the EPSPs in cortical neurons

Pdf available in bioRxiv

THANKS

FINANCIAL SUPPORT

ACKNOWLEDGEMENTS

Laboratório de Sistemas Neurais SisNe

Laboratório de Neurofisiologia e Sinapse