Role of PSD-95 in mouse binocular vision: A combined behavioural and 2-photon calcium imaging study
by Subhodeep Bhattacharya
English
Visual cortical circuits undergo a temporally restricted period of heightened plasticity early in neurodevelopment, termed the critical period (CP; Hubel and Wiesel, 1962, 1963). Crucial visual abilities, such as binocularity, are progressively shaped and optimised during this phase of maturation and refinement of the associated neuronal networks in the visual pathway (Cang et al., 2023). An important postsynaptic scaffolding protein, postsynaptic density 95 (PSD-95), has recently been observed to regulate the timely closure of CP for ocular dominance plasticity (ODP), wherein the proportion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) silent synapses substantially decreases during CP for ODP in the mouse primary visual cortex (V1; Huang et al., 2015). PSD-95 facilitates the unsilencing and maturation of AMPA-silent synapses, which are abundant in the juvenile visual cortex. The absence of PSD-95 in mice leads to persistently high proportions of AMPA-silent fractions, juvenile-like ODP, and aberrant spine dynamics, characterised by increased spine formation and elimination rates, after short-term (4-day) monocular deprivation (MD) even in late adulthood (Huang et al., 2015; Yusifov et al., 2021). At a behavioural level, PSD-95 knockout (KO) mice exhibit poor orientation discriminability despite normal visual acuity (Favaro et al., 2018). Given the development of binocularity coincides with CP for ODP (Wang et al., 2010; Tan et al., 2020, 2022), we hypothesised that PSD-95, and consequently, AMPA-silent synapse maturation would influence the development of binocular visual abilities. To investigate this, PSD-95 KO mice were tested for orientation discriminability using the visual water task (Favaro et al., 2018) and in prey capture behaviour, an ethologically relevant binocular visual task (Hoy et al., 2016). With binocular vision, gross deficits were observed in PSD-95 KO mice compared to WT mice in both orientation discrimination and diverse epochs of predation. Notably, with monocular vision, KO mice showed an observable improvement in both these behaviours, in contrast to the deterioration observed in monocular WT mice. The findings indicated the poor binocular behavioural performance to be an outcome of disturbed binocular integration of visual inputs due to the loss of PSD-95. To probe how binocular integration might be affected in the absence of PSD-95, repeated 2-photon Ca2+ imaging of layers 2/3 neurons of the binocular visual cortex (bV1) was conducted in awake head-fixed mice while being monocularly and binocularly presented with visual stimuli, consisting of static sinusoidal gratings of differing combinations of orientations, spatial frequencies and phases. Binocular bV1 neurons of KO mice exhibited a greater degree of binocular mismatch along with increased contralateral dominance and a more linear regime of binocular integration of visual inputs. While both monocular and binocular KO neurons consistently showed higher orientation selectivity compared to WT neurons, other receptive field properties of monocular neurons were largely similar across genotypes. Intriguingly, the preferred orientation of individual KO neurons remained stable over multiple days and exhibited less drift in the short-term timescale. Overall, the results presented in this thesis highlight the functional specificity of AMPA-silent synapse maturation in refining binocular vision, both in terms of binocular visual behaviour and the experience-dependent tuning and refinement of binocular bV1 neurons.
Keywords: binocular vision; PSD-95; silent synapses; critical period; predation; visual cortex; orientation tuning; binocular matching
Persistent Address:
http://dx.doi.org/10.53846/goediss-11581
