Cell type specific mechanisms for the refinement of receptive fields in developing visual cortex
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Cell type specific mechanisms for the refinement of receptive fields in developing visual cortex


The brain’s ability to resolve sensory information is limited by the receptive field properties of primary sensory neurons. Abnormal experience can disrupt receptive field refinement, sometimes causing irreversible damage to circuit function and visual behavior. Two cell types have been of strong interest in researching visual circuit development and plasticity: inhibitory neurons and microglia. Using transplantation, microglia depletion, and two-photon calcium imaging of developing neuronal populations, this thesis aims to better understand how inhibitory neurons and microglia contribute to the maturation of receptive fields in mouse V1.Inhibitory neurons contain multiple mechanisms important for the experience-dependent refinement of ocular dominance (OD) and spatial frequency selectivity in V1. Visual deprivation studies suggest patterned visual experience following eye-opening initiates inhibitory mechanisms that gate visual plasticity. However, recent transplantation studies in juveniles suggest that intrinsic mechanisms within inhibitory neurons gate the onset and closure of CP plasticity. To better understand the relationship between intrinsic inhibitory mechanisms and vision onset, we transplanted medial ganglionic eminence (MGE) inhibitory neurons into adult V1. We find MGE transplantation into adult V1 opens a new window of juvenile-like OD plasticity whose timing coincides with when the donor tissue would have had its window. Interestingly, transplant-induced CP window did not perturb receptive field properties in host neurons. However, in a mouse model of amblyopia, transplantation improved V1 selectivity for higher spatial frequencies. Thus, inhibitory neurons carry innate plasticity mechanisms that can be used to improve immature or aberrant V1 receptive field properties. In contrast to OD and spatial frequency selectivity, dark rearing experiments suggest vision onset guides the maturation of receptive field orientation selectivity in V1. To determine if the maturation of orientation selectivity in inhibitory neurons is similarly gated by innately timed mechanisms, we transplanted MGE cells into postnatal V1 and measured the orientation selectivity of receptive fields in host and transplanted neurons. We focused on the Parvalbumin-expressing inhibitory (PV) neuron whose receptive field maturation is most well understood. We find that the functional maturation of transplanted PV neurons is not affected by precocious light exposure. Instead, the maturation of PV orientation selectivity coincides with the days after transplantation (DAT) when the host would have had its receptive fields refined. Importantly, the orientation selectivity of host neurons was unaffected by the maturation state of transplanted PV. Thus, our data show PV inhibitory neuron mechanisms of growth and circuit integration must first be present for visual experience to shape receptive field properties. Microglia are widely suspected to play a crucial role in the structural remodeling of synapses correlated with the developmental refinement of neuronal activity. Perturbations of microglia physiology increases synapse numbers, alters membrane dynamics, and increases spontaneous activity. To determine the role of microglia on V1 receptive field refinement, we used the colony-stimulating factor-1 receptor (CSF1-R) inhibitor PLX5622 to rapidly ablate microglia starting in juveniles. Not surprisingly, the microglia depletion increased synapse umbers and elevated visually evoked activity across all V1 neurons. However, this did not alter neuronal coherence in V1. Moreover, microglia depletion did not prevent CP OD plasticity and the emergence of receptive fields with high spatial frequency selectivity. Instead, the functional consequences of microglia depletion were specific to and prevented the maturation of orientation selectivity in excitatory neurons. Together, our findings provide a compelling picture whereby innate inhibitory mechanisms permit visual experience to refine V1 receptive field properties with microglia as specific supporters of orientation selectivity.

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