An Intrinsic Neural Oscillator in the Degenerating Mouse Retina

Abstract

The loss of photoreceptors during retinal degeneration (RD) is known to lead to an increase in basal activity in remnant neural networks. To identify the source of activity, we combined two-photon imaging with patch-clamp techniques to examine the physiological properties of morphologically identified retinal neurons in a mouse model of RD (rd1). Analysis of activity in rd1 ganglion cells revealed sustained oscillatory (ϳ10 Hz) synaptic activity in ϳ30% of all classes of cells. Oscillatory activity persisted after putative inputs from residual photoreceptor, rod bipolar cell, and inhibitory amacrine cell synapses were pharmacologically blocked, suggesting that presynaptic cone bipolar cells were intrinsically active. Examination of presynaptic rd1 ON and OFF bipolar cells indicated that they rested at relatively negative potentials (less than Ϫ50 mV). However, in approximately half the cone bipolar cells, low-amplitude membrane oscillation (ϳ5 mV, ϳ10 Hz) were apparent. Such oscillations were also observed in AII amacrine cells. Oscillations in ON cone bipolar and AII amacrine cells exhibited a weak apparent voltage dependence and were resistant to blockade of synaptic receptors, suggesting that, as in wild-type retina, they form an electrically coupled network. In addition, oscillations were insensitive to blockers of voltage-gated Ca 2ϩ channels (0.5 mM Cd 2ϩ and 0.5 mM Ni 2ϩ ), ruling out known mechanisms that underlie oscillatory behavior in bipolar cells. Together, these results indicate that an electrically coupled network of ON cone bipolar/AII amacrine cells constitutes an intrinsic oscillator in the rd1 retina that is likely to drive synaptic activity in downstream circuits.

Sparse estimation of self-exciting point processes with application to LGN neural modeling

“…Another interesting observation made from Figure 5 is the high activity in the 85-95 ms range which corresponds to an intrinsic frequency of about 10-12 Hz. This is consistent with recent experiments showing that the LGN neurons have an intrinsic frequency of about 10 Hz [13]. Compared to the two-photon microscopy used previously, our method uses a short recording of spiking activity and signal processing techniques which is much more time and cost efficient.…”

mGluR6 deletion renders the TRPM1 channel in retina inactive

“…This idea further gains support from studies of bipolar cells in the rd retina. In this retina, the genetic composition of the rod bipolar machinery is intact, yet the mGluR6-related cascade proteins are incorrectly localized due to lack of photoreceptor input, and the rod bipolar cell remains hyperpolarized (Borowska et al 2011;Strettoi and Pignatelli 2000). Since perturbation of the rod-to-rod bipolar synapse leads to dispersion of several cascade proteins, including G␤ 5 , RGS11, and RGS7 (Cao et al 2008), the factor or protein that is crucial is not clear.…”

Early remodeling of müller cells in the rd/rd mouse model of retinal dystrophy

“…Electrophysiological measurements were obtained in whole-mount retina using a blind approach to target Mül-ler cells (Borowska et al, 2011). Müller cells were recognized by their characteristic IV relationships, which were dominated by K þ currents.…”