Heterogeneous Functional Organization of Somatostatin- and Dopamine-containing Wide-field Amacrine Cells in Mouse Retina
In the retina, somatostatin (SRIF) is an inhibitory neuropeptide that influences multiple cell types, including bipolar, amacrine and ganglion cells. SRIF is reported to have multiple cellular actions including modulation of the release of dopamine (DA) from tyrosine hydroxylase (TH)-containing amacrine cells; however, the cellular basis of this interaction is unknown. Using immunohistochemistry I showed SRIF- and TH-containing wide-field amacrine cells co-stratify in the OFF sublamina of the inner plexiform layer (IPL) adjacent to the inner nuclear layer (INL). These processes form a dense network, which co-ramify and make numerous contacts along their processes and at varicosities. SRIF- and TH-immunoreactive (IR) cell bodies and processes also contain GABA and vesicular GABA transporter (VGAT) immunoreactivity, and express the GABAA α3 receptor subunit. TH-IR cells also express the SRIF receptor subtype 2A (sst2A) and SRIF-IR cells express the D1 receptor. Calcium imaging recordings of Fluo-4 labeled TH-red fluorescent protein (TH-RFP) processes exhibited a ~40% decrease in fluorescent intensity following 60 mM [K+] depolarization in the presence of SRIF (100nM-100 μM) and L054264 (1-10μM), a selective sst2A agonist. These findings suggest a reciprocal relationship between these two amacrine cell types mediated by both feedback and feed forward actions. SRIF amacrine cells act at TH-containing amacrine cells by a paracrine mechanism at sst2A, as well as directly at GABAA receptors. TH amacrine cells likely act at SRIF-containing amacrine cells at D1 and GABAA receptors. This retinal microcircuit defines a novel modulatory relationship for SRIF and demonstrates its broad influence on multiple visual processes.