The visual thalamus of rodents has served as an important model for exploring the cellular and molecular mechanisms that underlie neural circuit formation. The overwhelming majority of these studies have focused on inputs to and projections from the dorsal lateral geniculate nucleus (dLGN). Relay neurons within dLGN receive strong glutamatergic inputs from retinal ganglion cells (RGCs) and serve as the principle conduit of visual signaling to the cortex. However, relay neurons do not act as passive relays of visual information. The gain of retinogeniculate signal transmission is modulated by nonretinal inputs to dLGN. These nonretinal inputs arise from visual cortex, pretectum, brainstem, thalamic reticular nuclei, and local dLGN interneurons, and they far outnumber the more powerful retinal inputs [1, 2]. In fact, nonretinal inputs account for as much as 95% of the nerve terminals in dLGN [1, 3–6].
Differences in the functional properties of inputs to dLGN translate into distinct neurochemical and ultrastructural differences in retinal and nonretinal synapses in dLGN. Retinal, cortical, brainstem and inhibitory nerve terminals in dLGN all contain distinct neurotransmitter synthesizing enzymes and synaptic vesicle associated transporter proteins necessary for their specific functions [4, 7–12]. At the ultrastructural level, several types of nerve terminals have been described in dLGN, defined by anatomical features such as terminal morphology, synaptic vesicle shape, and mitochondrial appearance [6, 13–16]. One set of nerve terminals contain flattened, oval shaped synaptic vesicles, a hallmark feature of inhibitory GABAergic terminals, and are therefore called F terminals [2, 14, 17]. In dLGN, GABAergic terminals arise from the thalamic reticular nucleus and local inhibitory interneurons [7, 18, 19]. Other classes of terminals in dLGN contain round (or rather spherical) synaptic vesicles, and these represent excitatory and modulatory inputs from the retina, cortex, brainstem, pretectum and superior colliculus . Glutamatergic retinal terminals are distinguished from all other round-vesicle containing terminals based on their exceptionally large size and pale-colored mitochondria [6, 13, 14, 20]. For this reason retinal terminals in dLGN are termed RLP terminals (for r ound synaptic vesicles, l arge terminal size, and p ale-colored mitochondria). In contrast, nonretinal excitatory/modulatory nerve terminals, which far outnumber RLPs, are termed RSD terminals for their round synaptic vesicles, small terminal size, and dark-colored mitochondria [3, 4, 6]. In addition to terminal size and mitochondrial appearance, retinal terminals in dLGN are distinguishable from other terminal types as they exhibit complex synaptic arrangements with F terminals, they cluster into complex synaptic zones encapsulated by glial processes (and arrangement termed a glomeruli), and they typically contain invaginations of spine-like structures from either dendrites of dLGN principle neurons or F terminals [2, 14, 20].
While synaptic organization and morphology in dLGN have been thoroughly explored, other retino-recipient regions of mouse thalamus have received far less attention. Adjacent to the dLGN are the ventral lateral geniculate nucleus (vLGN) and the intergeniculate leaflet (IGL), two thalamic nuclei that receive and process light derived information from the retina. It is important to note that while retinal axons innervate all regions of dLGN and IGL, only the external division of the rodent vLGN receives retinal afferent . For simplicity sake we will be referring to this external division of vLGN throughout this manuscript. In contrast to dLGN, which relays image-forming visual information to the primary visual cortex, vLGN and IGL contribute to functions of the non-image forming accessory visual system, such as irradiance detection, visuomotor responses, and circadian photo-entrainment [22, 23]. Source of inputs to vLGN and IGL are similar to that of dLGN, which includes inputs from retina, cortex, superior colliculus, thalamic reticular nucleus, and local interneurons [22, 24]. However, it is becoming increasingly clear that different classes of neurons from these nuclei project to distinct nuclei of visual thalamus. For example, while classes of image-forming RGCs, which transmit information regarding contrast, color and motion, project to dLGN, classes of non-image forming RGCs project to vLGN and IGL [23, 25–34]. Likewise, distinct classes of cortical neurons innervate dLGN and vLGN. Layer VI cortical neurons project to dLGN, whereas layer V cortical neurons project to vLGN [24, 35, 36]. In addition to differences in their inputs, projections from relay neurons in dLGN and vLGN widely differ. In contrast to the thalamocortical projections originating from dLGN, projections from vLGN do not enter cortex and instead innervate an array of ipsi- and contralateral structures within hypothalamus, thalamus and midbrain .
Despite this knowledge of the circuits associated with the more ventrally located nuclei of rodent visual thalamus, we lack important information regarding the organization, distribution and morphology of nerve terminals in this region. We therefore explored and compared the distribution, morphology and physiology of nerve terminals in vLGN and dLGN using immunolabeling, mouse genetics, anterograde axonal labeling, serial block face scanning electron microscope (SBFSEM) and whole-cell patch recordings. Our results show that nerve terminal composition not only differs between visual thalamic nuclei, but that, retinal terminal development, morphology and physiology also differ significantly in these nuclei.