Thenob2mouse, a null mutation inCacna1f: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses

Abstract

Glutamate release from photoreceptor terminals is controlled by voltage-dependent calcium channels (VDCCs). In humans, mutations in the Cacna1f gene, encoding the α 1F subunit of VDCCs, underlie the incomplete form of X-linked congenital stationary night blindness (CSNB2). These mutations impair synaptic transmission from rod and cone photoreceptors to bipolar cells. Here, we report anatomical and functional characterizations of the retina in the nob2 (no b-wave 2) mouse, a naturally occurring mutant caused by a null mutation in Cacna1f. Not surprisingly, the b-waves of both the light-and dark-adapted electroretinogram are abnormal in nob2 mice. The outer plexiform layer (OPL) is disorganized, with extension of ectopic neurites through the outer nuclear layer that originate from rod bipolar and horizontal cells, but not from hyperpolarizing bipolar cells. These ectopic neurites continue to express mGluR6, which is frequently associated with profiles that label with the

Deletion of the Presynaptic Scaffold CAST Reduces Active Zone Size in Rod Photoreceptors and Impairs Visual Processing

“…Sprouting of postsynaptic elements into the ONL with aberrant formation of synapses has been found in retinae of mouse mutants with impaired synaptic transmission (Haeseleer et al, 2004;Mansergh et al, 2005;Chang et al, 2006;Specht et al, 2007Specht et al, , 2009. Therefore, we investigated whether this was also the case in CAST Ϫ/Ϫ mice and could potentially contribute to the reduction of OPL width.…”

Functional and structural impact of the loss of the leucine-rich repeat protein LRIT1 in the mouse retina.

“…The exact synaptic location of PNA is unknown, but it is thought to be on the base of the cone terminal. Our observation that mGluR6 and PNA colocalize is consistent with previous studies (130). Prior studies have shown that GPR179 also colocalizes with PNA (25).…”

“…LRIT1 does not colocalize with the photoreceptor synaptic ribbon marker RIBEYE, but LRIT1 does reside within RIBEYE's crescents that mark rod terminals. Prior work has shown that the ON bipolar cell markers LRIT3 (78), NYX (63,73), mGluR6 (130), and TRPM1 (131) show a similar localization. Previous studies also showed that the horizontal cell markers calbindin and syntaxin-4 localize adjacent to piccolino or RIBEYE crescents, respectively (132,133).…”

Vesicular Glutamate Transporter 1 Is Required for Photoreceptor Synaptic Signaling But Not For Intrinsic Visual Functions

“…Mutations that cause disruption in photoreceptor signaling often result in the rearrangement of the processes of second-order neurons (Dick et al, 2003;Haeseleer et al, 2004;Chang et al, 2006). For example, in mice that are deficient for the presynaptic cytomatrix protein Bassoon, there is rearrangement of rod bipolar and horizontal dendrites, which is thought to be caused by a lack of photoreceptor-driven synaptic input (Dick et al, 2003).…”

“…Many knock-outs of synaptic molecules in the retina result in only partial loss of visual function (Dick et al, 2003;Chang et al, 2006;Duncan et al, 2006). VGLUT1-null mice could serve as a model to test development and function of not only the retina, but of the entire visual system.…”