Each featured original illustration from the early 1900s, is accompanied by a caption written to engage scientists, researchers and investigators who populate the NIH campus.  As well as a 3-D printed rendering that enlarges a detail of the illustration above.  In this way, the drawings are rendered more accessible to a variety of audiences—including vision-impaired visitors who can directly experience these tactile versions of Cajal's drawings.  These files are made available on the 3D Print Exchange.  Direct links to the 3-D print files are provided at the end of this page.

The Cajal illustrations currently on-view include:

• Auditory Tracts
• Axonal Tracts in Rat
• Cajal-Astrocytes
• Cajal Astrocytes
• Cerebral Cortex-ii
• Interneuronal Plexuses
• Medulla

Image Modified

Image Modified

Image Modified

Purkinje cells are the main source of cerebellar output, and as such, they must be tightly controlled to correctly regulate motor functions. Basket cells regulate the output of Purkinje cells through the Pinceau formation: fine, brush-like basket cell axons in contact with Purkinje cell bodies (shown above in c; the Purkinje cell bodies are indicated by the faint dotted lines). Cajal described them in 1888, when it was yet unproven that neurons were separate cells rather than an interconnected reticulum, and correctly noted that the basket cells and Purkinje cells were distinct entities. He also correctly noted that the Pinceau formation was an exception to his law of dynamic polarization, where information flows from the axons of one neuron to the dendrites of a neighboring neuron: the axons of both the basket cells and the Purkinje cells interact in the Pinceau formation. He did not, however, foresee the biological importance of the Pinceau formation, which we now know to be critical for normal motor function.

Image Modified

Cajal often used the olfactory system as a subject, finding it to be both easily accessible and regularly structured. Information derived from environmental stimuli that interact directly with olfactory receptors is transmitted to the main olfactory bulb (MOB) or accessory olfactory bulb (AOB) for processing before being transmitted deeper into the olfactory cortex. The MOB (B) receives input from the olfactory sensory neurons in the main olfactory epithelium, while the AOB (A) receives input from the vomeronasal organ via the vomeronasal nerve bundle (D). The AOB is thought to process input mainly from pheromones. Cajal noted that the AOB was composed of 4 layers: the glomerular layer (a), the mitral/tufted layer (b), the lateral olfactory tract (c), and the granular layer (d). Although the MOB and AOB shown above appear to be converging onto a common point, this is not the case – the mitral/tufted cells of the MOB synapse project to the main olfactory cortex, while the AOB mitral/tufted cells bypass the main olfactory cortex and project directly to the medial amygdala and hypothalamic nuclei.

Image Modified

Cajal’s fascination with the retina is well documented – his publications on retinal neurons and organization in various species span 45 years, the length of his career. While many of Cajal’s representations of the retina focus on the visual pathway and the directionality of signal flow, this figure depicting a cross section of the mammalian retina showcases the wide variety of cell types therein, particularly amacrine cells (f-n). While the direction of information flow was clear in photoreceptors (ñ and s), bipolar cells (not pictured here) and ganglion cells (o), amacrine cells and horizontal cells (a,b) seemed to defy his law of dynamic polarization. Cajal imagined that the retina transmitted visual information like a complete photograph up into the visual cortex. We now know that the retina actually transmits many photographs in parallel, each depicting specific qualities of the visual world. Horizontal and amacrine cells shape the spatial and temporal characteristics of these parallel images, enabling ganglion cells to encode complex information about color, contrast, motion and other visual features.

Image Modified

The superior temporal gyrus contains the auditory cortex, responsible for processing sound, and Wernicke’s area, which is necessary for the processing of speech to be understood as language rather than simply sounds. Shown here are several layers of pyramidal cells in the superior temporal gyrus, which is layered similarly to other areas of the temporal cortex. Though they vary in size and position, the pyramidal cells (a,b,c,d,e,f,g,h) all exhibit the characteristic cone-shaped cell body, a single apical dendrite extending upwards to the cortical surface, basal dendrites, and basal axons (a). Cajal characterized pyramidal cells from many tissues, detailing the variety of shapes and sizes found in different locations throughout the brain. He also hypothesized that size and shape of the dendritic arborizations of the pyramidal cells would vary over the lifespan of an organism depending; recent research reveals that the cells shown here, from the superior temporal gyrus of an infant, have much larger and denser dendritic branches than those from an adult would in this specific location.

Image Modified

The lenticular nucleus (E) is a lens-shaped bundle of neurons that, along with the caudate nucleus (R) and the internal capsule, comprises the corpus striatum.  Cajal used this drawing in his Texture of the Nervous System of Man and Vertebrates to illustrate the relatively large size of the lenticular nucleus in small mammals – in this case, a mouse – as compared to humans.  

Although Cajal posited that the corpus striatum in general was of decreasing evolutionary importance and only useful for the coordination of higher reflexes, we now know that it is important for the facilitation of voluntary movement.  The complexity and attention to detail in this drawing showcase Cajal’s skill in translating the view through his microscope lens to the page, where the structures he depicts are easily identifiable to today’s scientists more than 100 years after he put ink to paper.

Image Modified

Using the silver nitrate staining method to visualize these cells, he recognized that although the axons of the stellate neurons made numerous synapses with the Purkinje neuron cell bodies, they did not fuse at any point.  This supported his Neuron Doctrine, wherein the nervous system is composed of distinct cells rather than a network of continuously connected cells, and nervous impulses travel from the axon of one cell to the body of another.  

Although he first posited the Neuron Doctrine in 1894, it was not until the 1950s, when the first electron microscopes became available, that scientists were able to confirm the existence of the synapse and thus validate Cajal’s theory.

Image Modified

Astrocytes are a type of macroglia that are critical for maintaining physiological homeostasis in the CNS and supporting neuronal function.  Astrocytes in the grey and white matter of the brain typically have pedicles, or “feet”, that form contacts with capillaries (A, B, e) and control local blood flow.  

Using a uranium-nitrate technique specifically for staining astrocytes on a tissue sample bordering a cerebral wound, Cajal observed not only normal astrocytes in contact with capillaries, but also small amoeboid cells (a,b,c).  Other scientists, such as Alzheimer, had previously noted such cells in the CNS tissue of persons with various degenerative diseases, but their origins were uncertain.  Cajal correctly inferred that these cells were astrocytes which had somehow reshaped themselves after the injury.  

We now know that astrocytes become “reactive” after a brain injury: they become polarized, migrate, and their cell bodies swell.  Such reactive astrocytes are postulated to have both beneficial (wound healing, limitation of inflammation) and detrimental (scar formation) roles in the response to injury.

Image Modified

The gross anatomy and function of the visual system had been a subject of human curiosity for nearly 2000 years by the time Cajal made his careful studies of its constituent neurons in the early 1900s.  His meticulous eye allowed him to recognize and distinguish most of the neuronal cell types we recognize today, although he had only the morphology of the stained cells to guide him.  

He arranged his descriptions of the primary visual cortex, the first processing center for visual signals within the brain, according to 9 layers clearly delineated by the types of cells present.  A subset of these layers are shown above: medium pyramidal cells (B, D, F) in layer 6 give rise to recurrent axons (a) which reach back to the outermost layer of the cortex, while the giant pyramidal cells (A, E) in layer 7 form horizontal dendrite bundles as well as axons that descend into the lower layers of the cortex.  

Cajal was the first to realize how short the horizontal axonal/dendritic connections between the cells of the primary visual cortex were, and to hypothesize the significance of this fact: information flows vertically through the layers of the cortex with little lateral spread.

Image Modified

While neurogliaform cells do form some classical synapses, of the type that Cajal predicted, it is now known that many of their boutons do not have a specific post-synaptic target; instead, they are able to mediate mass-signal transmission to nearly any neuronal process within their axonal plexus using gamma-Aminobutyric acid.  Most modern research on neurogliaform cells has been performed on the hippocampus, where they are hypothesized to provide signaling cues to adult-born neurons.

Image Modified

The dorsal horn of the spinal cord contains an area known as both Rexed Lamina II and the substantia gelatinosa of Rolando, named for its gelatinous appearance due to a high concentration of small neurons and a lack of myelination.   Cajal classified the cells of the gelatinosa as either “limiting” (b, c) or “central” (d) according to their location within the area, their size, and their dendritic organization; modern neuroanatomists now classify the cells as “stalked” (b,c) or “islet”(d), although there are a variety of neurons in the gelatinosa that defy classification.  

Because the axons of many neurons in the gelatinosa appeared not to extend outside of the gelatinosa itself, it was once hypothesized that the gelatinosa was a “closed system;” we now know that neurons of the gelatinosa receive input from the spinothalamic tract and dorsal columns, and relay that information deeper into the spinal cord through Rexed Laminae III and IV.  

Neurons of the gelatinosa are unusually dense in Substance P and opioid-type pain receptors, and thus the gelatinosa is believed to play a role in the modulation/mediation of pain perception.

Image Modified

In this drawing from rat, Cajal shows signals from the interstitial nuclei (c,B) coming from the root of the oculomotor nerve (A), and being sent through the thalamus.  But experimental evidence in the past 25 years has revealed that these nuclei actually receive signals from the vestibular nuclei and send signals to the oculomotor nucleus through the posterior commissure (none of which appear in the plane of this illustration), so that information flows in the opposite direction than Cajal’s supposition.  

Moving the eye from its resting central position requires sustained movement of the extraocular muscles, but neurons that control various aspects of eye position encode only movement velocity. Consequently, signals must be integrated prior to reaching the oculomotor nucleus, a computation that occurs as they travel through the interstitial nuclei of Cajal.

Image Modified