Homeostatic Plasticity in the Visual Thalamus by Monocular Deprivation

Abstract

Monocular deprivation (MD) is a classic paradigm for experience-dependent cortical plasticity. One form is known as homeostatic plasticity, in which neurons innervated by the deprived eye show a remarkable capacity to compensate for degraded visual signals in an attempt to stabilize network activity. While the evidence supporting homeostatic plasticity in visual cortex is extensive, it remains unclear whether neurons in subcortical visual structures respond to MD in a similar manner. Here we examined if cells in the dorsal lateral geniculate nucleus (dLGN), the thalamic relay between the retina and visual cortex, show similar forms of experience-dependent homeostatic plasticity following MD. Two-week old mice were monocularly deprived for a period of 5-7 days and miniature excitatory postsynaptic currents (mEPSCs) were obtained from cells located in dLGN regions receiving input from the deprived or nondeprived eye. We found that MD promotes increases in the frequency and amplitude of mEPSCs, and were restricted to the monocular segment contralateral to the deprived eye. These changes were accompanied by an increase in the probability of glutamate release at corticothalamic terminals that arise from the deprived visual cortex. Our findings indicate that homeostatic synaptic regulation from MD extends beyond cortical circuitry and shed light on how the brain modulates and integrates activity in the face of altered sensory experience.

Retinal Input Regulates the Timing of Corticogeniculate Innervation

“…To determine when functional corticogeniculate synapses develop in dLGN, we made use of a parasagittal slice preparation in which corticothalamic fibers innervating dorsal thalamus are maintained (Turner and Salt, 1998;Krahe and Guido, 2011;Fig. 5E).…”

“…At the mature corticothalamic synapse, the EPSPs/EPSCs increase in amplitude in response to repetitive stimulation (Turner and Salt, 1998;Granseth et al, 2002;Granseth and Lindström, 2003;Alexander and Godwin, 2005;Kielland et al, 2006). To assess such facilitation, pairs of electrical stimuli were delivered with interstimulus intervals (ISIs) ranging from 100 to 1000 ms at stimulus intensities that were close to levels that evoked maximal amplitudes (Granseth et al, 2002;Granseth and Lindström, 2003;Krahe and Guido, 2011). The degree of facilitation was determined by calculating the paired pulse ratio (PPR), which is the amplitude of the second stimulus EPSP response (EPSP 2 ) divided by the amplitude of the first stimulus EPSP response (EPSP 1 ).…”

“…The deletion of math5, a transcription factor responsible for RGC differentiation, leads to a near complete loss of RGCs, the failure to form an optic nerve, and central targets that are devoid of retinal input (Brown et al, 2001;Wang et al, 2001;Wee et al, 2002;Brzezinski et al, 2005;Moshiri et al, 2008). Our rationale to employ the latter was to account for retinal signaling during embryonic ages (Godement et al, 1984) or inadvertent effects associated with mechanical damage or retinal degeneration (Eysel and Grüsser, 1978;Heumann and Rabinowicz, 1980;Dai et al, 2009;Lam et al, 2009). Figure 6A depicts coronal sections of dLGN from control, BE, and math5 Ϫ / Ϫ mice showing corticogeniculate projections visualized with -GFP.…”

An evolving view of retinogeniculate transmission

“…Both Hebbian and homeostatic mechanisms of synaptic plasticity have been shown to alter retinogeniculate synaptic strength during development (Mooney et al, 1993; Butts et al, 2007; Ziburkus et al, 2009; Krahe & Guido, 2011; Lin et al, 2014; Louros et al, 2014). High frequency stimulation of the optic tract, or low frequency stimulation coincident with postsynaptic depolarization in slices from immature ferret dLGN result in long-term enhancement of the EPSC, with contribution from NMDAR activation (Mooney et al, 1993).…”

“…Finally, plasticity rules based on burst timing have been identified before eye-opening (Butts et al, 2007 in rat), but these plasticity rules have not been examined in more mature slices. On the other hand, the contribution of homeostatic plasticity in retinogeniculate plasticity has been suggested through studies involving monocular deprivation, chronic dark rearing, manipulation of stargazin, and deletion of Mecp2 (a transcription factor necessary for homeostatic scaling up in the visual cortex; Blackman et al, 2012; Noutel et al, 2011; Krahe & Guido, 2011; Lin et al, 2014; Louros et al, 2014). Similar paradigms likely also drive synaptic plasticity at the fully mature retinogeniculate synapse.…”