Histamine receptors of cones and horizontal cells in Old World monkey retinas

Abstract

In primates the retina receives input from histaminergic neurons in the posterior hypothalamus that are active during the day. In order to understand how this input contributes to information processing in Old World monkey retinas, we have been localizing histamine receptors (HR) and studying the effects of histamine on the neurons that express them. Previously, we localized HR3 to the tips of ON bipolar cell dendrites and showed that histamine hyperpolarizes the cells via this receptor. We raised antisera against synthetic peptides corresponding to an extracellular domain of HR1 between the 4th and 5th transmembrane domains and to an intracellular domain near the carboxyl terminus of HR2. Using these, we localized HR1 to horizontal cells and a small number of amacrine cells and localized HR2 to puncta closely associated with synaptic ribbons inside cone pedicles. Consistent with this, HR1 mRNA was detected in horizontal cell perikarya and primary dendrites and HR2 mRNA was found in cone inner segments. We studied the effect of 5 µM exogenous histamine on primate cones in macaque retinal slices. Histamine reduced Ih at moderately hyperpolarized potentials, but not the maximal current. This would be expected to increase the operating range of cones and conserve ATP in bright, ambient light. Thus, all three major targets of histamine are in the outer plexiform layer, but the retinopetal axons containing histamine terminate in the inner plexiform layer. Taken together, the findings in these three studies suggest that histamine acts primarily via volume transmission in primate retina.

Membrane‐associated guanylate kinase scaffolds organize a horizontal cell synaptic complex restricted to invaginating contacts with photoreceptors

“…To determine whether SAP102 was localized to photoreceptor terminals, retinas were double‐labeled with antibodies to syntaxin 3, a membrane protein expressed by rods and cones that is a component of the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) complex at ribbon synapses (Morgans et al, ). Immunolabeling of syntaxin 3 is found in the membranes of cone and rod photoreceptor synaptic terminals (Li et al, ; Vila et al, ). Strong syntaxin 3 immunolabeling was found at the plasma membrane of synaptic terminals in rods (Fig.…”

“…The SAP102-IR puncta were always located above ON bipolar cell dendrites (mGluR6) in rods and slightly above OFF bipolar cell basal contacts (GluR5) in cones. Scale bars 5 5 lm in B (applies to A,B); 5 lm in C-F. photoreceptor synaptic terminals (Li et al, 2009;Vila et al, 2012). Strong syntaxin 3 immunolabeling was found at the plasma membrane of synaptic terminals in rods (Fig.…”

What optogenetic stimulation is telling us (and failing to tell us) about fast neurotransmitters and neuromodulators in brain circuits for wake–sleep regulation

“…The onset of the effects of photo-released histamine was slow (1-3 min) and persisted long after the stimulation was completed (10-15 min). Based on the onset delay, kinetics, and duration of the responses to photostimulation of the TMN neurons, histamine appears to act via volume transmission [75-77]. In addition, the action on synaptic inputs would suggest that once released, histamine might diffuse a short distance to activate H3 receptors in the TMN region and H1 receptors in VLPO, acting on presynaptic terminals of afferent inputs to TMN and VLPO neurons.…”

The Role of Histamine in the Retina: Studies on the Hdc Knockout Mouse

“…Rather, sparse retinopetal axons arising from the tuberomammillary nucleus extend across the inner plexiform layer eliciting responses in a range of inner retinal neurons [11] – [13] . Histamine receptors, H 1 R, H 2 R, H 3 R have been localized to subsets of inner retinal neurons in rodent and primate retinae [13] , [14] . In particular, circuits important in mediating scotopic vision, may be altered by histamine release.…”

“…To date there have been no reports of retinal changes or functional anomalies in the Hdc −/− mouse. Based on the expression and distribution of histamine receptors within the retina [13] , [14] , and the functional evidence that some retinal neurons are modulated by histamine [12] , it is likely that the Hdc −/− mouse has a retinal phenotype.…”