Requirements for synaptically evoked plateau potentials in relay cells of the dorsal lateral geniculate nucleus of the mouse

Abstract

Non-technical summary In the developing visual system, spontaneous retinal activity plays an important role in the refinement of retinal ganglion cell projections to the dorsal lateral geniculate nucleus (dLGN) of thalamus. How such changes are implemented remains unknown. Recordings of post-synaptic dLGN cell activity suggest that plateau-like, L-type Ca 2+ channel-mediated depolarizations figure prominently in remodelling. Plateaus are developmentally regulated and their incidence is controlled by the changing patterns of excitatory and inhibitory connections onto dLGN cells. At early ages there is a high degree of retinal convergence, and excitatory post-synaptic events summate to produce depolarizations sufficient to activate plateaus. As these excitatory inputs are pruned and inhibitory connections emerge, the net excitatory drive is reduced and plateaus wane. Additionally, L-type channels are highly expressed at young ages, and subunit disruptions resulting in decreased expression also affect the incidence of plateaus. These studies help elucidate the mechanisms underlying activity-dependent refinement of sensory connections.Abstract In developing cells of the mouse dorsal lateral geniculate nucleus (dLGN), synaptic responses evoked by optic tract (OT) stimulation give rise to long-lasting, high-amplitude depolarizations known as plateau potentials. These events are mediated by L-type Ca 2+ channels and occur during early postnatal life, a time when retinogeniculate connections are remodelling. To better understand the relationship between L-type activity and dLGN development we used an in vitro thalamic slice preparation which preserves the retinal connections and intrinsic circuitry in dLGN and examined how synaptic responses evoked by OT stimulation lead to the activation of plateau potentials. By varying the strength and temporal frequency of OT stimulation we identified at least three factors that contribute to the developmental regulation of plateau activity: the degree of retinal convergence, the temporal pattern of retinal stimulation and the emergence of feed-forward inhibition. Before natural eye opening (postnatal day 14), the excitatory synaptic responses of relay cells receiving multiple retinal inputs summated in both the spatial and temporal domains to produce depolarizations sufficient to activate L-type activity. After eye opening, when inhibitory responses are fully developed, plateau activity was rarely evoked even with high temporal rates of OT stimulation. When the bulk of this inhibition was blocked by bath application of bicuculline, the incidence of plateau activity increased significantly. We also made use of a transgenic mouse that lacks the β 3 subunit of the L-type Ca 2+ channel. These mutants have far fewer membrane-bound Ca 2+ channels and attenuated L-type activity. In β 3 nulls, L-type plateau activity was rarely observed even at young ages when plateau activity prevails. Thus, in addition to the changing patterns of synaptic connectivity and retinal activity,

Homeostatic Plasticity in the Visual Thalamus by Monocular Deprivation

“…MD also had no effect on the input/out relations associated with OT stimulation (Figure 7). In both normal and deprived cases, a progressive increase in stimulus intensity gave rise to step-like increases in amplitude, indicating that dLGN cells at these ages receive input from just a few retinal ganglion cells (Chen and Regehr 2000; Jaubert-Miazza et al 2005; Dilger et al, 2011). …”

“…Slices were prepared in a manner similar to previous reports (Bickford et al, 2010; Dilger et al, 2011). Animals were deeply anesthetized with isoflurane and decapitated.…”

Postnatal development of cholinergic input to the thalamic reticular nucleus of the mouse

“…During recordings, the tissue was visualized using DIC optics on a microscope equipped with a 10× objective, a 60× water immersion objective (Olympus), and a CCD camera (Olympus Y‐150), using previously described methods (Dilger et al ., ). EYFP was visualized with a fluorescent light source through a Chroma filter using a 10× or 60× objective.…”

“…The final tip resistance of patch electrodes was 8–12 MΩ. Whole‐cell current and voltage clamp recordings were made using Multiclamp 700B amplifier (Molecular Devices), filtered at 3–10 kHz, and digitized (Digidata 1440A) using techniques described elsewhere (Dilger et al ., ; Jurgens et al ., ; Seabrook et al ., ). Recordings were conducted in neurons with resting membrane potential between −55 and −75 mV and series resistance between 10 and 25 MΩ.…”

Inhibitory circuits for visual processing in thalamus

“…For example, retinal input to interneurons often targets distal, electronically remote dendrites [53*]. Studies in vitro show that retinal drive activates L-type calcium currents [68,69*] that transmit depolarization to the soma and evoke spikes at variable delay [69*]. .…”