Stuart Mangel, Ph.D. March 27, 2015Professor, Dept. of NeuroscienceE-mail: [email protected]; 2-5753
BIOPHYSICS 6702 – ENCODING NEURAL INFORMATION IN THE RETINA AND BRAIN
I. Basic Features of Principal Retinal Circuits a. photoreceptor cells hyperpolarize to light b. horizontal cells hyperpolarize to light (sign-conserving synapse) c. Depolarizing and hyperpolarizing bipolar cells (sign-conserving and sign-inverting
synapses) d. Receptive field structure of bipolar cells (center-surround organization; horizontal
cells provide receptive field surround using lateral inhibition) e. Receptive field structure of ganglion cells (generation of action potentials; center-
surround organization; perceived brightness contrast) f. Parallel processing (“trigger” features; non-linear response mechanisms)
- amacrine cells (e.g. starburst amacrine cells)- ganglion cells (e.g. transient vs. sustained; directionally selective, etc.)
On-Bipolar Cells
Stimulus
Spot
(Center)
Horizontal CellsOff-Bipolar Cells
Annulus
(Surround)
Spot + Annulus
Horizontal cells provide the receptive field surround to bipolar cells
Synaptic connections that produce the center-surround receptive field organization of bipolar cells
Bipolar cell receptive field
OFF-BC: Hyperpol
ON-BC: Depol
OFF-BC: Depol
ON-BC: Hyperpol
Cones hyperpolarize
Cones hyperpolarize
Horizontal cellshyperpolarize
Light stimulation over small, central
retinal area
Light stimulation over larger, surrounding
retinal area
excitatory (“sign-conserving”) synapse
inhibitory (“sign-inverting”) synapse
Synaptic connections that produce the center-surround receptive field organization of bipolar cells
Bipolar cell receptive field
OFF-BC: Hyperpol
ON-BC: Depol
OFF-BC: Depol
ON-BC: Hyperpol
Cones hyperpolarize
Cones Depolarize
Cones hyperpolarize
Horizontal cellshyperpolarize
Light stimulation over small, central
retinal area
Light stimulation over larger, surrounding
retinal area
excitatory (“sign-conserving”) synapse
inhibitory (“sign-inverting”) synapse
Na+K+2Cl-
GABA
Cl-
GABAA
receptor
Na-K-2Cl (NKCC)
GABA-Evoked Depolarization
K+ Cl-
GABA
GABAA
receptor
Cl-
K-Cl (KCC)
GABA-Evoked Hyperpolarization
Cl-
ON-BC DENDRITE OFF-BC DENDRITE
1. The GABA released from horizontal cells depolarizes ON-BC dendrites, but hyperpolarizes OFF-BC dendrites. 2. The chloride cotransporters, Na-K-2Cl (NKCC) and K-Cl (KCC), determine whether GABAA receptor activation, which opens Cl- channels, depolarizes or hyperpolarizes neurons, respectively.
Cl-
Receptive field profiles of ganglion cell subtypes
X-type ganglion cell
Y-type ganglion cell
- from Barlow and Levick, 1965
ON-OFF direction selective ganglion cells
Response properties of ON-OFF direction selective ganglion cells
Models of direction selectivity in the retina
ROLE OF ION TRANSPORTERS IN NEURAL NETWORK FUNCTION
Fig. 2. The dendrites of starburst amacrine cells (green), a type of interneuron in the retina, hyperpolarize to light stimuli that move from the periphery to the cell body (bottom left) and depolarize to light stimuli that move from the cell body to the periphery (bottom right). These directionally-selective responses are generated in part by the differential distribution of the Na-K-2Cl (NKCC) cotransporter (pink) on the cell body and proximal dendrites and the K-Cl (KCC2) cotransporter (blue) on the distal dendrites. The expression patterns of Na-K-2Cl and K-Cl are represented as pink to purple and purple to blue gradients, respectively, on the dendrites and cell body of this starburst cell.
GABA-evoked depolarization
GABA-evoked hyperpolarization
Fig. 1. The chloride cotransporters, Na-K-2Cl (NKCC) and K-Cl (KCC2), determine whether the neurotransmitter GABA, which opens Cl- channels, depolarizes or hyperpolarizes neurons, respectively.
Fig. 1
Fig. 2
- modified from Gavrikov et al., 2006, PNAS
Fig. 3. The GABA reversal potential at the starburst amacrine cell (SAC) distal dendrite is more hyperpolarized than at the proximal dendrite due to KCC2 activity. (A, B) GABA was applied onto the proximal dendrite (A) and onto the distal dendrite (B) ~ 100 m from the cell body of a SAC in the presence of cobalt (2 mM) to block synaptic transmission. (C) Average EGABA of the proximal and distal dendrites of SACs were significantly different (p < 0.01). (D) Average EGABA of distal dendrites before and during bath application of FUR (25 M), a selective inhibitor of KCC2 activity, were significantly different (p < 0.01).
Fig. 3
A MODEL OF DIRECTION SELECTIVITY IN THE RETINA
- modified from Gavrikov et al., 2003, PNAS
Ribelayga, Cao & Mangel, 2008, Neuron
Rod pathways at night under dark conditions
The circadian (24-hr) clock in the retina increases the electrical coupling of rod-cone gap junctions at night
Readings for Biophysics 6702 – Lectures on March 25/27, 2015:
Kandel, Schwartz, Jessell, Siegelbaum & Hudspeth, 2013, Principles of Neural Science, 5th Ed., Chapters 21, 26
Masland, 2004, Direction Selectivity
Gavrikov, Nilson, Dmitriev, Zucker & Mangel, 2006, PNAS
Fried, Munch & Werblin, 2002, Nature