Van Hooser, S. D. | bioRxiv Science

bioRxiv2017

Rem2 regulates distinct homeostatic mechanisms in visual circuit plasticity

Activity-regulated genes sculpt neural circuits in response to sensory experience. These calcium-sensitive genes generally fall into two categories: transcription factors and proteins that function at synapses. Yet little is known about activity-regulated, cytosolic proteins that transduce signals between the neuronal membrane and the nucleus. Using the visual system as a model, we investigated the role of the activity-regulated, non-canonical Ras-like GTPase Rem2 in vivo. We demonstrate that Rem2-/- mice fail to exhibit normal ocular dominance plasticity during the critical period. At the circuit level, cortical layer 2/3 neurons in Rem2-/- mice show deficits in both postsynaptic scaling up of excitatory synapses and misregulation of intrinsic excitability. Further, we reveal that Rem2 plays a novel, cell-autonomous role in regulating neuronal intrinsic excitability. Thus, Rem2 is a critical regulator of neural circuit function and distinct homeostatic plasticity mechanisms in vivo.\n\nHIGHLIGHTSO_LIRem2 is required in excitatory cortical neurons for normal ocular dominance plasticity\nC_LIO_LIRem2 regulates postsynaptic homoeostatic synaptic scaling up\nC_LIO_LIRem2 alters the intrinsic excitability of neurons in a cell-autonomous manner\nC_LI

neuroscience↗

bioRxiv2017

Development of cross-orientation suppression and size tuning and the role of experience

Many sensory neural circuits exhibit response normalization, which occurs when the response of a neuron to a combination of multiple stimuli is less than the sum of the responses to the individual stimuli presented alone. In the visual cortex, normalization takes the forms of cross-orientation suppression and surround suppression. At the onset of visual experience, visual circuits are partially developed and exhibit some mature features such as orientation selectivity, but it is unknown whether cross-orientation suppression or surround suppression are present at the onset of visual experience or require visual experience for their emergence. We characterized the development of these properties and their dependence on visual experience in ferrets. Visual experience was varied across three conditions: typical rearing, dark rearing, and dark rearing with daily exposure to simple sinusoidal gratings (14-16 hours total). Cross-orientation suppression and surround suppression were noted in the earliest observations, and did not vary considerably with experience. We also observed evidence of continued maturation of receptive field properties in the second month of visual experience: substantial length summation was observed only in the oldest animals (postnatal day 90); evoked firing rates were greatly increased in older animals; and direction selectivity required experience, but declined slightly in older animals. These results constrain the space of possible circuit implementations of these features.\n\nSignificance StatementThe development of the brain depends on both nature - factors that are independent of the experience of an individual animal - and nurture - factors that depend on experience. While orientation selectivity, one of the major response properties of neurons in visual cortex, is already present at the onset of visual experience, it is unknown if response properties that depend on interactions among multiple stimuli develop without experience. We find that the properties of crossorientation suppression and surround suppression are present at eye opening, and do not depend on visual experience. Our results are consistent with the idea that a majority of the basic properties of sensory neurons in primary visual cortex are derived independent of the experience of an individual animal.

neuroscience↗