Developmental Homeostasis of Mouse Retinocollicular Synapses

Abstract

) that lack correlated waves, retinocollicular map refinement is impaired. In vivo recordings reveal that neurons in the superior colliculus of ␤2 Ϫ/Ϫ mice have large receptive fields and low peak visual responses, resulting in a conservation of total integrated response. We find that this "response homeostasis" is maintained on a cell-bycell basis, and argue that it does not depend on regulation from the visual cortex during adulthood. Instead, in vitro recordings show that homeostasis arises from the conservation of total synaptic input from the retina, and that it is maintained via different mechanisms over development. In the absence of correlated retinal waves, ␤2Ϫ/Ϫ neurons sample a larger number of weaker retinal inputs relative to controls after the first postnatal week. Once retinal waves are restored, developmental learning rules and homeostasis drive refinement so that fewer, stronger synapses are retained, as in wild-type mice, but from a larger retinal area. Homeostasis in neurons has been shown previously to regulate the gain of synaptic transmission in response to perturbations of activity. Our results suggest that during the development of sensory maps, a unique consequence of homeostatic mechanisms is the precise shaping of neuronal receptive fields in conjunction with activity-dependent competition.

Homeostatic Regulation of Intrinsic Excitability and Synaptic Transmission in a Developing Visual Circuit

“…Similar observations have been made in immature visual cortex, where mEPSC frequency is inversely correlated with amplitude (Desai et al, 2002), and in the superior colliculus, where RGC inputs are weak in neurons that receive input from a large number of RGCs, whereas RGC inputs are stronger in neurons receiving input from few RGCs (Chandrasekaran et al, 2007). This observation suggests that EPSC amplitude is not necessarily the best indicator of total synaptic drive, because we see a developmental increase in total synaptic drive despite a decrease in sEPSC amplitude.…”

Retinocollicular Synapse Maturation and Plasticity Are Regulated by Correlated Retinal Waves

“…This supports the hypothesis that synaptic competition stabilizes developing axons and eliminates inappropriate connections in mammals as well. We previously showed that ␤2 Ϫ/Ϫ synapses at P6 -P7 are not only weaker but also greater in number relative to control synapses (Chandrasekaran et al, 2007). Correlated presynaptic activity, therefore, may be the necessary upstream signal for synaptic learning rules to strengthen appropriate synapses and eliminate inappropriate inputs.…”

“…Number of cells is written adjacent to each group. P6 -P7 data points come from Chandrasekaran et al (2007). In control synapses, there is a developmental increase in AMPA/NMDA ratios from P3-P4 to P6 -P7 (**p Ͻ 0.01).…”

“…The distributions are shown for control (gray lines) and ␤2 Ϫ/Ϫ (black lines) experiments at P3-P4 (C 1 ), P6 -P7 (C 2 ), and P12-P13 (C 3 ). P6 -P7 data comes from Chandrasekaran et al (2007). Note the leftward shift in the probability distributions for the ␤2 Ϫ/Ϫ group at P6 -P7 relative to the control group, indicating a greater percentage of small amplitude events.…”

Prostaglandin E2-Induced Synaptic Plasticity in Neocortical Networks of Organotypic Slice Cultures

“…Homeostatic plasticity is critical for maintaining stability in neuronal networks involved in various physiological processes, including neurodevelopment (Chandrasekaran et al, 2007) and learning and memory (Nelson and Turrigiano, 2008). In response to changes in synaptic strength, homeostatic plasticity reestablishes a fine balance between excitation and inhibition.…”