Types Of Projection Neurons Research Articles

Parallel processing of working memory and temporal information by distinct types of cortical projection neurons

It is unclear how different types of cortical projection neurons work together to support diverse cortical functions. We examined the discharge characteristics and inactivation effects of intratelencephalic (IT) and pyramidal tract (PT) neurons—two major types of cortical excitatory neurons that project to cortical and subcortical structures, respectively—in the deep layer of the medial prefrontal cortex in mice performing a delayed response task. We found stronger target-dependent firing of IT than PT neurons during the delay period. We also found the inactivation of IT neurons, but not PT neurons, impairs behavioral performance. In contrast, PT neurons carry more temporal information than IT neurons during the delay period. Our results indicate a division of labor between IT and PT projection neurons in the prefrontal cortex for the maintenance of working memory and for tracking the passage of time, respectively.

Progenitor cell diversity in the developing mouse neocortex

In the mammalian neocortex, projection neuron types are sequentially generated by the same pool of neural progenitors. How neuron type specification is related to developmental timing remains unclear. To determine whether temporal gene expression in neural progenitors correlates with neuron type specification, we performed single-cell RNA sequencing (scRNA-Seq) analysis of the developing mouse neocortex. We uncovered neuroepithelial cell enriched genes such as Hmga2 and Ccnd1 when compared to radial glial cells (RGCs). RGCs display dynamic gene expression over time; for instance, early RGCs express higher levels of Hes5, and late RGCs show higher expression of Pou3f2 Interestingly, intermediate progenitor cell marker gene Eomes coexpresses temporally with known neuronal identity genes at different developmental stages, though mostly in postmitotic cells. Our results delineate neural progenitor cell diversity in the developing mouse neocortex and support that neuronal identity genes are transcriptionally evident in Eomes-positive cells.

Temporal evolution of single-cell transcriptomes of Drosophila olfactory projection neurons.

Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological properties. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes of Drosophila olfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage-neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types.

Cortical direct current stimulation improves signal transmission between the motor cortices of rats

Transcranial direct current (DC) stimulation is a noninvasive brain stimulation technique that is now widely used to improve motor and cognitive function. The neuromodulatory effects of DC is considered to extend to nearby as well as remote brain areas from the site of stimulation because of current flowing into the brain and/or signal transmission in neuronal networks. However, the effects of DC on cortico-cortical neuronal transmission are not well known. In the present study, we focused on signal transmission from the primary (M1) to secondary (M2) motor cortex of rats. Intra-cortical microstimulation (ICMS) was applied to the M1 under DC conditions, and changes in synaptic activity in the M2 were examined using current-source density analyses. The synaptic input to the M2 superficial layers was enhanced during DC stimulation, while the synaptic input to the M2 deeper layers was increased after DC stimulation. These results suggest that DC stimulation improves cortico-cortical neuronal transmission from M1 to M2, and that the effectiveness of DC may be different among different projection neuron types in the M1.

Antennal-lobe neurons in the moth Helicoverpa armigera: Morphological features of projection neurons, local interneurons, and centrifugal neurons.

The relatively large primary olfactory center of the insect brain, the antennal lobe (AL), contains several heterogeneous neuronal types. These include projection neurons (PNs), providing olfactory information to higher‐order neuropils via parallel pathways, and local interneurons (LNs), which provide lateral processing within the AL. In addition, various types of centrifugal neurons (CNs) offer top‐down modulation onto the other AL neurons. By performing iontophoretic intracellular staining, we collected a large number of AL neurons in the moth, Helicoverpa armigera, to examine the distinct morphological features of PNs, LNs, and CNs. We characterize 190 AL neurons. These were allocated to 25 distinct neuronal types or sub‐types, which were reconstructed and placed into a reference brain. In addition to six PN types comprising 15 sub‐types, three LN and seven CN types were identified. High‐resolution confocal images allowed us to analyze AL innervations of the various reported neurons, which demonstrated that all PNs innervating ventroposterior glomeruli contact a protocerebral neuropil rarely targeted by other PNs, that is the posteriorlateral protocerebrum. We also discuss the functional roles of the distinct CNs, which included several previously uncharacterized types, likely involved in computations spanning from multisensory processing to olfactory feedback signalization into the AL.

Transcription factor expression defines subclasses of developing projection neurons highly similar to single-cell RNA-seq subtypes.

We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than 50 unique types of mature cortical projection neurons defined by their distinct gene-expression profiles. Moreover, exactly how and when neurons diversify their function during development is unknown. Here we relate gene expression and chromatin accessibility of two subclasses of projection neurons with divergent morphological and functional features as they develop in the mouse brain between embryonic day 13 and postnatal day 5 in order to identify transcriptional networks that diversify neuron cell fate. We compare these gene-expression profiles with published profiles of single cells isolated from similar populations and establish that layer-defined cell classes encompass cell subtypes and developmental trajectories identified using single-cell sequencing. Given the depth of our sequencing, we identify groups of transcription factors with particularly dense subclass-specific regulation and subclass-enriched transcription factor binding motifs. We also describe transcription factor-adjacent long noncoding RNAs that define each subclass and validate the function of Myt1l in balancing the ratio of the two subclasses in vitro. Our multidimensional approach supports an evolving model of progressive restriction of cell fate competence through inherited transcriptional identities.

Neuronal diversity, dendro-spinous characterization in the hippocampal complex of Coracias benghalensis

Coracias benghalensis, a seasonally breeding sub-tropical bird, displays a peculiar rolling behavior to attract the female for courtship and territoriality. The avian hippocampal complex (HCC) is a dorsomedial component of the forebrain and is involved in cognitive functions and sexual behavior. The present study was aimed to identify and characterize the neuronal classes, dendritic arborization, and spines density in the HCC of C. benghalensis during the quiescent phase of the breeding cycle. Adult male birds were collected during the winter season from a wild zone of Prayagraj (25?? 28??? N, 81?? 54??? E), U.P., India. These birds were transcardially perfused, and whole brains were stained with Cresyl-violet and Golgi-Colonnier staining method. We observed unipolar, bipolar, pyramidal, and multipolar types of projection neurons and local circuit (aspinous) neurons with a qualitative and quantitative characterization of soma size, dendritic arborization, and spine density. The multipolar neurons with the highest spine density were predominantly present in the HCC of C. benghalensis. This study concludes that the bird???s neuronal diversity and neuronal characteristics suggest a unique character that helps the bird perform overt rolling behavior as functional (learning and memory) intervention of the HCC.

Neurogenesis of medium spiny neurons in the nucleus accumbens continues into adulthood and is enhanced by pathological pain

In mammals, most adult neural stem cells (NSCs) are located in the ventricular–subventricular zone (V-SVZ) along the wall of the lateral ventricles and they are the source of olfactory bulb interneurons. Adult NSCs exhibit an apico-basal polarity; they harbor a short apical process and a long basal process, reminiscent of radial glia morphology. In the adult mouse brain, we detected extremely long radial glia-like fibers that originate from the anterior–ventral V-SVZ and that are directed to the ventral striatum. Interestingly, a fraction of adult V-SVZ-derived neuroblasts dispersed in close association with the radial glia-like fibers in the nucleus accumbens (NAc). Using several in vivo mouse models, we show that newborn neurons integrate into preexisting circuits in the NAc where they mature as medium spiny neurons (MSNs), i.e., a type of projection neurons formerly believed to be generated only during embryonic development. Moreover, we found that the number of newborn neurons in the NAc is dynamically regulated by persistent pain, suggesting that adult neurogenesis of MSNs is an experience-modulated process.

Expression of cannabinoid CB1 R-GPR55 heteromers in neuronal subtypes of the Macaca fascicularis striatum.

The cannabinoid CB1 receptor (CB1 R) is the most abundant G protein-coupled receptor in the central nervous system, consistent with the important role of endocannabinoids as neuromodulators. Cannabinoids also modulate the function of G protein-coupled receptor 55 (GPR55), which forms heteroreceptor complexes with the CB1 R in the striatum. The aim was to characterize cannabinoid CB1 R-GPR55 heteromers (CB1 R/GPR55Hets) in the basal ganglia input nuclei of nonhuman primates, Macaca fascicularis, both in projection neurons and interneurons, by the in situ proximity ligation assay. Striatal projecting neurons were identified by the retrograde neuroanatomical tracer, biotinylated dextran amine (BDA), injected into external or internal subdivisions of the globus pallidus. Triple immunofluorescent stains were carried out to visualize (1) BDA-labeled neurons, (2) CB1 R/GPR55Hets, and (3) striatal interneurons positive for choline acetyltransferase, parvalbumin, calretinin, or nitric oxide synthase. CB1 R/GPR55Hets were identified within both types of projection neurons as well as all interneurons except those that are cholinergic. Moreover, CB1 R/GPR55Hets were found specifically in the neuronal cell surface, and also in intracellular membranes. Further research efforts will be needed to confirm the intracellular occurrence of heteromers and their potential as therapeutic targets in diseases related to motor control imbalances, particularly within a parkinsonian context (with or without levodopa-induced dyskinesia).

Ephrin-B2 paces neuronal production in the developing neocortex

BackgroundDuring mammalian cerebral cortex development, different types of projection neurons are produced in a precise temporal order and in stereotypical numbers. The mechanisms regulating timely generation of neocortex projection neurons and ensuring production in sufficient numbers of each neuronal identity are only partially understood.ResultsHere, we show that ephrin-B2, a member of the Eph:ephrin cell-to-cell communication pathway, sets the neurogenic tempo in the neocortex. Indeed, conditional mutant embryos for ephrin-B2 exhibit a transient delay in neurogenesis and acute stimulation of Eph signaling by in utero injection of synthetic ephrin-B2 led to a transient increase in neuronal production. Using genetic approaches we show that ephrin-B2 acts on neural progenitors to control their differentiation in a juxtacrine manner. Unexpectedly, we observed that perinatal neuron numbers recovered following both loss and gain of ephrin-B2, highlighting the ability of neural progenitors to adapt their behavior to the state of the system in order to produce stereotypical numbers of neurons.ConclusionsAltogether, our data uncover a role for ephrin-B2 in embryonic neurogenesis and emphasize the plasticity of neuronal production in the neocortex.

The microcircuits of striatum in silico

The basal ganglia play an important role in decision making and selection of action primarily based on input from cortex, thalamus, and the dopamine system. Their main input structure, striatum, is central to this process. It consists of two types of projection neurons, together representing 95% of the neurons, and 5% of interneurons, among which are the cholinergic, fast-spiking, and low threshold-spiking subtypes. The membrane properties, soma-dendritic shape, and intrastriatal and extrastriatal synaptic interactions of these neurons are quite well described in the mouse, and therefore they can be simulated in sufficient detail to capture their intrinsic properties, as well as the connectivity. We focus on simulation at the striatal cellular/microcircuit level, in which the molecular/subcellular and systems levels meet. We present a nearly full-scale model of the mouse striatum using available data on synaptic connectivity, cellular morphology, and electrophysiological properties to create a microcircuit mimicking the real network. A striatal volume is populated with reconstructed neuronal morphologies with appropriate cell densities, and then we connect neurons together based on appositions between neurites as possible synapses and constrain them further with available connectivity data. Moreover, we simulate a subset of the striatum involving 10,000 neurons, with input from cortex, thalamus, and the dopamine system, as a proof of principle. Simulation at this biological scale should serve as an invaluable tool to understand the mode of operation of this complex structure. This platform will be updated with new data and expanded to simulate the entire striatum.

Canine Adenovirus 2: A Natural Choice for Brain Circuit Dissection.

Canine adenovirus-2 (CAV) is a canine pathogen that has been used in a variety of applications, from vaccines against more infectious strains of CAV to treatments for neurological disorders. With recent engineering, CAV has become a natural choice for neuroscientists dissecting the connectivity and function of brain circuits. Specifically, as a reliable genetic vector with minimal immunogenic and cytotoxic reactivity, CAV has been used for the retrograde transduction of various types of projection neurons. Consequently, CAV is particularly useful when studying the anatomy and functions of long-range projections. Moreover, combining CAV with conditional expression and transsynaptic tracing results in the ability to study circuits with cell- and/or projection-type specificity. Lastly, with the well-documented knowledge of viral transduction, new innovations have been developed to increase the transduction efficiency of CAV and circumvent its tropism, expanding the potential of CAV for circuit analysis.

The chick pallium displays divergent expression patterns of chick orthologues of mammalian neocortical deep layer-specific genes

The avian pallium is organised into clusters of neurons and does not have layered structures such as those seen in the mammalian neocortex. The evolutionary relationship between sub-regions of avian pallium and layers of mammalian neocortex remains unclear. One hypothesis, based on the similarities in neural connections of the motor output neurons that project to sub-pallial targets, proposed the cell-type homology between brainstem projection neurons in neocortex layers 5 or 6 (L5/6) and those in the avian arcopallium. Recent studies have suggested that gene expression patterns are associated with neural connection patterns, which supports the cell-type homology hypothesis. However, a limited number of genes were used in these studies. Here, we showed that chick orthologues of mammalian L5/6-specific genes, nuclear receptor subfamily 4 group A member 2 and connective tissue growth factor, were strongly expressed in the arcopallium. However, other chick orthologues of L5/6-specific genes were primarily expressed in regions other than the arcopallium. Our results do not fully support the cell-type homology hypothesis. This suggests that the cell types of brainstem projection neurons are not conserved between the avian arcopallium and the mammalian neocortex L5/6. Our findings may help understand the evolution of pallium between birds and mammals.

Retinotopic specializations of cortical and thalamic inputs to area MT

Retinotopic specializations in the ventral visual stream, especially foveal adaptations, provide primates with high-acuity vision in the central visual field. However, visual field specializations have not been studied in the dorsal visual stream, dedicated to processing visual motion and visually guided behaviors. To investigate this, we injected retrograde neuronal tracers occupying the whole visuotopic representation of the middle temporal (MT) visual area in marmoset monkeys and studied the distribution and morphology of the afferent primary visual cortex (V1) projections. Contrary to previous reports, we found a heterogeneous population of V1-MT projecting neurons distributed in layers 3C and 6. In layer 3C, spiny stellate neurons were distributed mainly in foveal representations, while pyramidal morphologies were characteristic of peripheral eccentricities. This primate adaptation of the V1 to MT pathway is arranged in a way that we had not previously understood, with abundant stellate projection neurons in the high-resolution foveal portions, suggesting rapid relay of motion information to visual area MT. We also describe that the medial portion of the inferior pulvinar (PIm), which is the main thalamic input to area MT, shows a retinotopic organization, likely reflecting the importance of this pathway during development and the establishment of area MT topography.

Separate But Interactive Parallel Olfactory Processing Streams Governed by Different Types of GABAergic Feedback Neurons in the Mushroom Body of a Basal Insect.

The basic organization of the olfactory system has been the subject of extensive studies in vertebrates and invertebrates. In many animals, GABA-ergic neurons inhibit spike activities of higher-order olfactory neurons and help sparsening of their odor representations. In the cockroach, two different types of GABA-immunoreactive interneurons (calyceal giants [CGs]) mainly project to the base and lip regions of the calyces (input areas) of the mushroom body (MB), a second-order olfactory center. The base and lip regions receive axon terminals of two different types of projection neurons, which receive synapses from different classes of olfactory sensory neurons (OSNs), and receive dendrites of different classes of Kenyon cells, MB intrinsic neurons. We performed intracellular recordings from pairs of CGs and MB output neurons (MBONs) of male American cockroaches, the latter receiving synapses from Kenyon cells, and we found that a CG receives excitatory synapses from an MBON and that odor responses of the MBON are changed by current injection into the CG. Such feedback effects, however, were often weak or absent in pairs of neurons that belong to different streams, suggesting parallel organization of the recurrent pathways, although interactions between different streams were also evident. Cross-covariance analysis of the spike activities of CGs and MBONs suggested that odor stimulation produces synchronized spike activities in MBONs and then in CGs. We suggest that there are separate but interactive parallel streams to process odors detected by different OSNs throughout the olfactory processing system in cockroaches.SIGNIFICANCE STATEMENT Organizational principles of the olfactory system have been the subject of extensive studies. In cockroaches, signals from olfactory sensory neurons (OSNs) in two different classes of sensilla are sent to two different classes of projection neurons, which terminate in different areas of the mushroom body (MB), each area having dendrites of different classes of MB intrinsic neurons (Kenyon cells) and terminations of different classes of GABAergic neurons. Physiological and morphological assessments derived from simultaneous intracellular recordings/stainings from GABAergic neurons and MB output neurons suggested that GABAergic neurons play feedback roles and that odors detected by OSNs are processed in separate but interactive processing streams throughout the central olfactory system.

Sensory cortex wiring requires preselection of short- and long-range projection neurons through an Egr-Foxg1-COUP-TFI network

The bimodal requisite for a genetic program and external stimuli is a key feature of sensory circuit formation. However, the contribution of cell-intrinsic codes to directing sensory-specific circuits remains unknown. Here, we identify the earliest molecular program that preselects projection neuron types in the sensory neocortex. Mechanistically, Foxg1 binds to an H3K4me1-enriched enhancer site to repress COUP-TFI, where ectopic acquisition of Foxg1 in layer 4 cells transforms local projection neurons to callosal projection neurons with pyramidal morphologies. Removal of Foxg1 in long-range projection neurons, in turn, derepresses COUP-TFI and activates a layer 4 neuron-specific program. The earliest segregation of projection subtypes is achieved through repression of Foxg1 in layer 4 precursors by early growth response genes, the major targets of the transforming growth factor-β signaling pathway. These findings describe the earliest cortex-intrinsic program that restricts neuronal connectivity in sensory circuits, a fundamental step towards the acquisition of mammalian perceptual behavior.

Three divisions of the mouse caudal striatum differ in the proportions of dopamine D1 and D2 receptor-expressing cells, distribution of dopaminergic axons, and composition of cholinergic and GABAergic interneurons

The greater part of the striatum is composed of striosomes and matrix compartments, but we recently demonstrated the presence of a region that has a distinct structural organization in the ventral half of the mouse caudal striatum (Miyamoto et al. in Brain Struct Funct 223:4275–4291, 2018). This region, termed the tri-laminar part based upon its differential immunoreactivities for substance P and enkephalin, consists of medial, intermediate, and lateral divisions. In this study, we quantitatively analyzed the distributions of both projection neurons and interneurons in each division using immunohistochemistry. Two types of projection neurons expressing either the dopamine D1 receptor (D1R) or D2 receptor (D2R) showed complementary distributions throughout the tri-laminar part, but the proportions significantly differed among the three divisions. The proportion of D1R-expressing neurons in the medial, intermediate, and lateral divisions was 88.6 ± 8.2% (651 cells from 3 mice), 14.7 ± 3.8% (1025 cells), and 49.3 ± 4.5% (873 cells), respectively. The intermediate division was further characterized by poor innervation of tyrosine hydroxylase immunoreactive axons. The numerical density of choline acetyltransferase immunoreactive neurons differed among the three divisions following the order from the medial to lateral divisions. In contrast, PV-positive somata were distributed throughout all three divisions at a constant density. Two types of GABAergic interneurons labeled for nitric oxide synthase and calretinin showed the highest cell density in the medial division. The present results characterize the three divisions of the mouse caudal striatum as distinct structures, which will facilitate studies of novel functional loops in the basal ganglia.

Morphological Cell Types Projecting from V1 Layer 4B to V2 Thick and Thin Stripes.

In macaque visual cortex, different cytochrome oxidase stripes of area V2 receive segregated projections from layers (L)2/3 and 4B of the primary visual cortex (V1), and project to dorsal or ventral stream extrastriate areas. Parallel V1-to-V2 pathways suggest functionally specialized circuits, but it is unknown whether these circuits arise from distinct cell types. V1 L4B includes two morphological types of excitatory projection neurons: pyramids, which carry mixed magnocellular (M) and parvocellular (P) information to downstream areas, and spiny stellates, which carry only M information. Previous studies have shown that, overall, V2 receives ∼80% of its L4B inputs from pyramids, thus receiving mixed M and P signals. However, it is unknown how pyramids and stellates distribute their outputs to the different V2 stripes, and whether different stripes receive inputs from morphologically distinct neuron types. Using viral-mediated labeling of V2-projecting L4B neurons in male macaques, we show that thick stripes receive a greater contribution of L4B inputs from M-dominated spiny stellates compared with thin stripes. Both stripe types, however, receive a much larger contribution from spiny stellates than previously shown for V2 overall, indicating that a larger amount of M information than previously thought flows into both the dorsal and ventral streams via the V2 thick and thin stripes, respectively. Moreover, we identify four types of V2-projecting L4B cells differing in size and complexity. Three such cell types project to both thin and thick stripes, but one type, the giant spiny-stellate neuron, resembling L4B neurons projecting to motion-sensitive area MT, was only found to project to thick stripes.SIGNIFICANCE STATEMENT Area V1 partitions visual information into functionally specialized parallel pathways which terminate into distinct stripes of area V2. We asked whether V1 inputs to different V2 stripes arise from morphologically different cell types. V1 layer (L)4B has two cell types: pyramids, which carry both magnocellular (M) and parvocellular (P) visual signals, and spiny stellates, which carry only M signals. We find that V2 thick stripes, which project to areas processing object motion, receive a larger fraction of L4B input from M-dominated stellates compared with thin stripes, which project to areas processing object attributes. We also identify four morphological types of V2-projecting L4B neurons, suggestive of four functionally specialized cell types.

Multiple Patterns of Axonal Collateralization of Single Layer III Neurons of the Rat Presubiculum.

The presubiculum plays a key role in processing and integrating spatial and head-directional information. Layer III neurons of the presubiculum provide strong projections to the superficial layers of the medial entorhinal cortex (MEC) in the rat. Our previous study revealed that the terminal distribution of efferents from layer III cells of the presubiculum was organized in a band-like fashion within the MEC, and the transverse axis of these zones ran parallel to the rhinal fissure. Identifying axonal branching patterns of layer III neurons of the presubiculum is important to further elucidate the functional roles of the presubiculum. In the present study, we visualized all axonal processes and terminal distributions of single presubicular layer III neurons in the rat, using in vivo injection of a viral vector expressing membrane-targeted palmitoylation site-attached green fluorescent protein (GFP). We found that layer III of the rat presubiculum comprised multiple types of neurons (n = 12) with characteristic patterns of axonal collateralization, including cortical projection neurons (n = 6) and several types of intrinsic connectional neurons (n = 6). Two of six cortical projection neurons provided two or three major axonal branches to the MEC and formed elaborate terminal arbors within the superficial layers of the MEC. The width and axis of the area of their terminal distribution resembled that of the band-like terminal field seen in our massive-scale observation. Two of the other four cortical projection neurons gave off axonal branches to the MEC and also to the subiculum, and each of the other two neurons sent axons to the subiculum or parasubiculum. Patterns of axonal arborization of six intrinsic connectional neurons were distinct from each other, with four neurons sending many axonal branches to both superficial and deep layers of the presubiculum and the other two neurons showing sparse axonal branches with terminations confined to layers III–V of the presubiculum. These data demonstrate that layer III of the rat presubiculum consists of multiple types of cortical projection neurons and interneurons, and also suggest that inputs from a single presubicular layer III neuron can directly affect a band-like zone of the MEC.

Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina

High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.