Functionally intact glutamate-mediated signaling in bipolar cells of the TRKB knockout mouse retina

Abstract

In the juvenile trkB knockout (trkB −/− ) mouse, retina synaptic communication from rods to bipolar cells is severely compromised as evidenced by a complete absence of electroretinogram (ERG) bwave, even though the inner retina appears anatomically normal (Rohrer et al., 1999). Since it is well known that the b-wave reflects light-dependent synaptic activation of ON bipolar cells via their metabotropic glutamate receptor, mGluR6, we sought to analyze the anatomical and functional integrity of the glutamatergic synapses at these and other bipolar cells in the trkB −/− mouse. Although rod bipolar cells from wild-type juvenile mice were determined to be immunopositive for trkB, postsynaptic metabotropic and ionotropic glutamate receptor-mediated pathways in ON and OFF bipolar cells were found to be functionally intact, based on patch electrode recordings, using brief applications ("puffs") of glutamate or its analog, 2-amino-4-phosphonobutyric acid (APB), a selective agonist for mGluR6 receptors. Ionotropic glutamate receptor function was assayed in OFFcone bipolar and horizontal cells by applying exogenous glutamatergic agonists in the presence of the channel-permeant guanidinium analogue, 1-amino-4-guanidobutane (AGB). Electronmicroscopic analysis revealed that the ribbon synapses between rods and postsynaptic rod bipolar and horizontal cells were formed at the appropriate age and appear to be structurally intact, and immunohistochemical analysis did not detect profound defects in the expression of excitatory amino acid transporters involved in glutamate clearance from the synaptic cleft. These data indicate that there does not appear to be evidence for postsynaptic deficits in glutamatergic signaling in the ON and OFF bipolar cells of mice lacking trkB.

Trpm1

“…On the other hand, light stimulation on both wild-type (WT) and Trpm1 À/À mice cone OFF-bipolar cells evoked photoresponses, and there were no significant differences in either the amplitude of the light responses or the time for half-maximal amplitude after the light was turned off (Koike et al 2010b). Examination of the optokinetic responses and electroretinograms (ERGs) of 2-month-old WT and Trpm1 À/À mice revealed optokinetic deficiencies similar to those of mice lacking mGluR6 and WT mice injected intravitreally with the mGluR6 agonist, L-2 amino-4-phosphonobutyric acid (Slaughter and Miller 1985;Euler et al 1996;Iwakabe et al 1997;McGillem and Dacheux 2001;Rohrer et al 2004;Koike et al 2010b). The ERGs evoked by light stimuli in WT mice show normal a-waves and b-waves, originating mainly from photoreceptor cells and bipolar cells, respectively.…”

Tetrodotoxin‐resistant voltage‐gated sodium channels Nav1.8 and Nav1.9 are expressed in the retina

“…Whereas BDNF may be produced and released in the retina by Müller glial cells (Seki et al,2003,2005), trk B receptors have not previously been observed to be expressed by photoreceptors (Rohrer et al,1999; Liu et al,2007). It is interesting to note, however, that homozygous trk B knockout mice have a robust electroretinography (ERG) a‐wave, but lack the ERG b‐wave, suggesting a failure in photoreceptor neurotransmission (Rohrer et al,1999,2004). Regardless of the mechanism, VGSCs have been recently implicated to play a major role in cone photoreceptor physiology.…”

Cysteamine Attenuates the Decreases in TrkB Protein Levels and the Anxiety/Depression-Like Behaviors in Mice Induced by Corticosterone Treatment

“…TrkB knockout (TrkB -/- ) mice were provided by Dr. Barbara Rohrer, Medical University of South Carolina, Charleston, SC and the colony was maintained in our animal housing facility at the Georgia Health Sciences University. The generation of mice lacking the TrkB has been described previously [29]. Male wild-type (WT) and TrkB -/- mice (C57BL/6 strain background) used in a given experiment, originated from the same breeding series and were matched for age and weight (age = 2–3 months; weight = 25–30 g).…”