ON and OFF retinal ganglion cells differentially regulate serotonergic and GABAergic activity in the dorsal raphe nucleus

Abstract

The dorsal raphe nucleus (DRN), the major source of serotonergic input to the forebrain, receives excitatory input from the retina that can modulate serotonin levels and depressive-like behavior. In the Mongolian gerbil, retinal ganglion cells (RGCs) with alpha-like morphological and Y-like physiological properties innervate the DRN with ON DRN-projecting RGCs out numbering OFF DRN-projecting RGCs. The DRN neurons targeted by ON and OFF RGCs are unknown. To explore retino-raphe anatomical organization, retinal afferents labeled with Cholera toxin B were examined for association with the postsynaptic protein PSD-95. Synaptic associations between retinal afferents and DRN serotonergic and GABAergic neurons were observed. To explore retino-raphe functional organization, light-evoked c-fos expression was examined. Light significantly increased the number of DRN serotonergic and GABAergic cells expressing c-Fos. When ON RGCs were rendered silent while enhancing the firing rate of OFF RGCs, c-Fos expression was greatly increased in DRN serotonergic neurons suggesting that OFF DRN-projecting RGCs predominately activate serotonergic neurons whereas ON DRN-projecting RGCs mainly target GABAergic neurons. Direct glutamatergic retinal input to DRN 5-HT neurons contributes to the complex excitatory drive regulating these cells. Light, via the retinoraphe pathway can modify DRN 5-HT neuron activity which may play a role in modulating affective behavior.

Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells

“…Figure 2E2 shows an example of ON and OFF RGC membrane potentials in response to 500 ms of light stimulation. The HFS-induced neuromodulation (Figure 2E1 ) elicited preferential excitation in a manner similar to the differential activation of ON and OFF RGCs that occurs physiologically following a light stimulus (Figure 2E2 ), and reported ON and OFF RGC response to light (Wang et al, 2001 ; Zhang et al, 2016 ; Tsai et al, 2017 ). All of these results illustrated the potential for artificial retinal stimulation to mimic natural RGC encoding.…”

Neuroanatomical Relationships between Orexin/Hypocretin-Containing Neurons/Nerve Fibers and Nicotine-Induced c-Fos-Activated Cells of the Reward-Addiction Neurocircuitry

“…Among these regions, DR exhibits the most intense orexinergic innervation. DR is a heterogeneous structure that contains multiple other cell types including serotonergic, GABAergic and glutamatergic neurons [ 31 , 32 ]. Thus, intense orexinergic innervation of this site, as demonstrated in the present study, implies that other cell types are the potential targets of orexin at DR.…”

A retinoraphe projection regulates serotonergic activity and looming-evoked defensive behaviour

“…Revealing the structure and function of the precise circuit related to the DRN is important for the understanding of how the serotonergic system exerts its influence upon defensive responses. The DRN in several species including primates receives retinal afferents and DRN-projecting retinal ganglion cells (RGCs) regulate serotonergic signalling in the brain2122. It is worth noting that in the Mongolian gerbil DRN-projecting RGCs also send collateral branches to the SC23.…”