Introduction to the Nervous System 4 At 1.5 cm crown-rump length, in lateral view, the brain of the cat looks as shown in Figure 1. It would not be much different in appearance in the dog. Fig. 1. Lateral view of neural tube of cat, 1.5 cm crown-rump length. From Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. brain spinal cord But the brain of a mature dog looks like this: brain spinal cord Fig. 2. Canine brain, lateral view. The main theme of this presentation is how we get from Fig. 1 to Fig. 2. Lamina terminalis, growth of the hemispheres. With the neural tube formed and its neuropores closed off at either end, the tube and the neural crest beside it rest in a sea of mesoderm filled with cells and the intercellular substance that the cells have formed. The tube is large at its anterior end, which will form the brain, and tapers by an elongate developing spinal cord to its sealed posterior end. The anterior end of the tube is the lamina terminalis of the adult brain. Right and left hemispheres (the telencephalon) outpouch dorsolaterally from this anterior end, incorporating an extension of the lumen of the tube, which will become the lateral ventricle of each. The surrounding mesoderm differentiates to form the meninges and the fluid-filled subarachnoid space. Fig. 3.. Neural tube, 1 cm CR length, median section. From Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. Fig. 4. Neural tube, diagrammatic. Dorsal view with hemispheres and ventricular system further developed. lamina terminalis outpouching hemisphere outpouching hemisphere lamina terminalis Fig. 5. Median section of mature canine brain, showing the position of the lamina terminalis. The orange arrow passes through the interventricular foramen into the lateral ventricle. lamina terminalis Ventricular system, meninges, choroid plexus. The ventricular system of the brain and cord results from the variable enlargement and extension of the lumen of the neural tube. Diagrammatically: olfactory bulb of hemisphere Fig. 6. The drawing is from Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: hemisphere (telencephalon) diencephalon (thalamic portions) mesencephalon (midbrain) metencephalon (pons, cerebellum) rhombencephalon myelencephalon (medulla oblongata) medulla spinalis (spinal cord) 1 3 2 CAq 4 CeCa Ventricles 1 and 2 are the lateral ventricles, one in each hemisphere; the lateral ventricle is curved, like the hemisphere. A slender extension from the anterior end of the lateral ventricle passes anteriorly in the olfactory stalk to a small chamber within the olfactory bulb. Each lateral ventricle communicates with the 3rd ventricle by way of the interventricular foramen. The third ventricle is central between the thalamic nuclei of each side. It completely separates R and L thalamic nuclei until their growth results in a median interthalamic adhesion. The adhesion is central and converts the undivided chamber into a circular one. No crossing of fibers or intermixing of right and left side cells occurs at the adhesion. From the 3rd ventricle, the cerebral (mesencephalic) aqueduct, a narrow passage, extends posteriorly to the 4th ventricle. The 4th ventricle is a large chamber within the rhombencephalon (metencephalon + myelencephalon). At its posterior end, the obex of the 4th ventricle, the chamber is continuous with the central canal of the spinal cord. Figs. 7, A, B. show the growth of the thalamic nuclei to form the interthalamic adhesion, converting the undivided 3rd ventricle to a circular chamber: Figs. 7, A, B. Both figures (the B figure has been modified slightly) are from Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. A is a median section through the developing brain of a 1.6 cm CR length cat embryo; B is a growing thalamic nuclei X infundibular recess A interventricular foramen lamina terminalis optic recess Interthalamic adhesion rd 3 ventricle B Above (dorsal to) the pons, the roof of the fourth ventricle becomes thicker and folded, growimg to form the cerebellum. Anterior and posterior to the developing cerebellum, the roof remains as a thin covering: the anterior and posterior medullary vela. Fig. 8. Neural tube, 1 cm CR length, median section. From Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. 4th ventricle roof of 4th ventricle prior to growth of the cerebellum Fig. 9. Cat, 1.6 cm CR length, median section showing beginning development of the cerebellum and the medullary vela. From Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. anterior medullary velum cerebellum X 4th ventricle Fig. 10. Dorsal view of canine brain with much of the dorsal part of the hemispheres cut away. The roof of the third ventricle is removed. The cerebellum and most of the vela are removed; the 4th ventricle is exposed. posterior medullary velum posterior colliculus anterior medullary velum (cut) 4th ventr. posterior medullary velum (cut) Fig. 11. Median section through the canine brain. The anterior half of the cerebellum and the anterior medullary velum are indicated. mesencephalic aqueduct anterior medullary velum 4th ventricle Meninges and choroid plexus. The meninges arise by differentiation of the mesenchyme surrounding the neural tube. They are connective tissue membranes that condense around the brain and spinal cord with sleeve-like extensions that envelop the roots of the spinal nerves and the spinal ganglia. At the spinal ganglion, the membranes fuse together and are continuous with the connective tissue of the ganglion and the epineurium of the spinal nerve. From within outward there are three meninges, the pia mater, arachnoid mater, and dura mater. In the guinea pig, the arachnoid mater has been shown to be an artifactually created membrane brought about by separation (fracturing) of the light-cell layer of the dura (see The Subdural Space Interpreted as a Cellular Layer of Meninges, Richard D. Frederickson, Anat. Rec., 230, 38-51 1991). We treat the two membranes as an inseparable duraarachnoid. Between the dura-arachnoid mater and the pia mater is the subarachnoid space, which is lined by a mesothelium and filled with cerebrospinal fluid (CSF). The CSF functions, in part, in providing a fluid cushion for the brain and cord. The subarachnoid space communicates with the ventricular space at the lateral aperture of each of the lateral recesses of the fourth ventricle. The opening is just dorsal to the acoustic tubercle and ventral to the choroid plexus of the fourth ventricle. In humans, there is often a median, third, aperture at the posterior end of the fourth ventricle. Fig. 12. Canine brain. Dorsal view of 4th ventricle, showing its lateral recesses. acoustic tubercle vestibulocochlear (VIIIth cranial) nerve nerve 4th ventr. lateral recess Fig. 13. Lateral view of canine brain, left hemisphere removed. Arrow points to the position of the lateral aperture between the acoustic tubercle and the choroid plexus. choroid plexus The pia mater is a loose, chiefly collagenous, connective tissue intimately applied to the surface of the brain and spinal cord with a thin layer passing with the vessels that penetrate the nervous tissue. The larger vessels upon the surface of the brain and cord also pass within a thin layer of the pia mater. A mesothelium is applied to its surface that faces the subarachnoid space. Numerous isolated slender bundles of fibers, arachnoid trabeculae, clothed with a mesothelium, pass between the deep surface of the dura-arachnoid and the deeper lying pia. Fig. 14. The meninges at brain level. From http://vanat.cvm.umn.edu/neurHistAtls/pages/images/Men1.jpg . subarachnoid space Choroid plexuses, structure and topography. The choroid plexus elaborates the cerebrospinal fluid. Each choroid plexus is composed of 1. A network of vessels that develops in relation to specific parts of the walls of the lateral, third, and fourth ventricles, 2. The tela choroidea, the web-like connective tissue supporting the capillaries of the vascular network, and 3. A simple layer of cuboidal ependymal cells that faces the lumen of the ventricle and secretes the cerebrospinal fluid. In the area where the plexus develops, the neural tube thins to a single ependymal cell layer. The ependymal cells are joined by occluding junctions, which assure that the composition of the CSF is regulated by the ependymal cells. (ependyma) Fig. 15. Choroid plexus from the developing brain, lateral ventricle, of the cat; A, low power, B, about100x. From: Ronald A. Bergman, Ph.D., Adel K. Afifi, M.D., Paul M. Heidger, Jr., Ph.D. www.anatomyatlases.org/MicroscopicAnatomy/Section06/Plate06132.shtml Choroid plexuses of the lateral and third ventricles. Choroid plexuses are present in each lateral ventricle, in the roof of the third ventricle, and, as a pair, in the roof of the fourth ventricle. Each plexus of the lateral ventricle develops as a delicate infolding of its medial wall along the line of the hemisphere’s joining the diencephalon (this is at the stria terminalis, which marks the junction). At the level of the interventricular foramen each choroid plexus of the lateral ventricle joins the choroid plexus of the third ventricle. This is shown in the two figures that follow; Martin’s diagrams are only slightly modified from the original. Fig. 16. Cross-section through the brain at the level of the developing interthalamic adhesion. Diagrammatic. From Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. choroid plexus of the third ventricle hemisphere choroid plexus of the lateral ventricle, formed from a thinning and infolding of the ventricular wall thalamus Fig. 17. Cross-section through the brain, lateral showing the continuity ventricle of choroid plexuses of lateral and third ventricles at the level of the interventricular foramen. Diagrammatic. From Lehrbuch der Anatomie der Haustiere, Paul interventricular Martin, 1912: foramen Schickhardt & Ebner, The following figures show the topography of the choroid plexuses of lateral and third Stuttgart. third ventricle ventricles in the mature equine brain. The arrangement is similar in the human brain and all of the mammals that we study. The fold of choroid plexus of each lateral ventricle, which is a part of the wall of the ventricle, extends from the stria terminalis at the junction of the hemisphere with the thalamus to the lateral edge of the fimbria of the hippocampus and the fornix of the hemisphere.The figures are taken from Guide for the Laboratory Examination of the Anatomy of the Horse, A. Horowitz, 1965; University Bookstore, The Ohio State University. Fig. 18A. Brain, dorsal aspect with roof of the lateral ventricles (corpus callosum) removed. The position of the subcortical nuclei of the right hemisphere is indicated. The representation of the nuclei is taken from Neuroanatomy, A Programmed Text by Sidman and Sidman, Little, Brown and Company. Fig. 18B. Brain, dorsal aspect. Structures forming the floor of the lateral ventricle are cut posteriorly and reflected forward to reveal the underlying thalamus, midbrain, anterior cerebellum, and choroid plexuses of 3rd and lateral ventricles.. choroid plexus of the lateral ventricle (yellow) Interventricular foramen fornix A B Choroid plexuses of 4th ventricle, arachnoid granulations, cerebrospinal fluid flow. The choroid plexuses of the 4th ventricle are paired, right and left. A part of the plexus is prolapsed from the lateral aperture and rests in the subarachnoid space ventral to the posterior cerebellum. See Figs. 19 and 20. Fig. 19. Canine brain with the cerebellum removed to show the choroid plexuses of the 4th ventricle. R, L choroid plexuses, prolapsed part VIIIth cranial nerve posterior medullary velum R and L choroid plexuses (from the deep side of the medullary velum) Fig. 20. Cross-section through the 4th ventricle at the level of the lateral aperture. Diagrammatic. choroid plexus, prolapsed part lateral aperture acoustic tubercle R and L choroid plexuses (from the deep side of the 4th ventriclefluid is elaborated by the choroid plexuses and is thought to be Cerebrospinal medullary velum) absorbed 1. (presumably) by the arachnoid granulations of the arachnoid membrane, 2. by lymphatic vessels of the spinal and cranial nerves, and 3. by way of the olfactory nerves and the lymphatic vessels of the nasal cavity. The arachnoid granulations are evaginations of the arachnoidea (arachnoid mater) that perforate the dura and the wall of a venous sinus to end blindly in the lumen of the sinus where they are thought (this is not universally accepted) to secrete cerebrospinal fluid into the bloodstream. Fig. 21. Diagram of the arachnoid granulations. From: http://instruct.uwo.ca/anatomy/530/530notes.htm A brief explanation of terms: Venous sinuses are veins that lack valves and are without smooth muscle in their walls. Dural venous sinuses are veins found between the folds of the cranial dura mater or between the cranial dura and the periosteum of the cranial vault (some authors describe this periosteum as the “dural periosteum” or the “periosteal layer of the dura”). The veins that proceed from the brain capillaries pass upon the brain’s surface in relation to the pia mater, which provides a thin covering (see Fig. 14). They are designated cerebral and cerebellar veins and pass in the subarachnoid space to perforate the dura and discharge into a dural venous sinus. The dural venous sinuses are drained by emissary veins that pass through the different skull foramina to discharge in the extracranial veins, chiefly tributaries of the internal and external jugular veins. Normal flow of the CSF. In the normal case, CSF produced by the choroid plexuses flows freely from its origin, passes out the lateral apertures into the subararachnoid space, and is absorbed at the arachnoid granulations and by way of the lymphatic vessels of the spinal and cranial nerves and of the nasal mucosa. The CSF normally maintains a maximum pressure of about 86.5 mm water (dog) to 379 mm (horse). An increased pressure with accumulation of fluid results when there is a blockage in the path of flow (non-communicating hydrocephalus) or a failure of adequate absorption (communicating hydrocephalus). The mesencephalic aqueduct is the most common site of blockage. Fig. 22. Ventricular system, dog. Corpus callosum, hippocampus, and fornix. The corpus callosum, the largest of the commissures joining the right and left halves of the brain, first appears as a rounded bundle of fibers at the dorsal part of the lamina terminalis. With addition of fibers by interposition and apposition, it grows posteriorly and its form is altered according to the growth of the hemisphere. It develops a curvature, the splenium, that follows the growth and form of the posterior hemisphere. In the dog, growth of the hemisphere and addition of fibers rostrally results in the separation of the corpus callosum from the lamina terminalis. In all mammals, there is a development of an anterior curvature, the genu. In some species, equine and bovine, for example, and in humans, a more slender band of fibers extends ventrocaudally from the genu, retaining the connection of the genu to the lamina terminalis. This part is designated the rostrum of the corpus callosum. The writer has not observed rostrum fibers in the dog. The body (truncus) of the corpus callosum is elongate, between the genu and splenium, and is its largest part. The part of the medial hemisphere enclosed by the curvature of the corpus callosum becomes the septum pellucidum. According to Martin (1912), sometimes the two hemispheres fuse in this area, sometimes not. With absence of fusion, a space remains, the cavum septi. Fig. 23. Martin’s original figure of a median section (at the level of the lamina terminalis) of a 4 cm crown rump length cat embryo. From Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. fiber-bundle of beginning corpus callosum olfactory bulb lamina terminalis, somewhat thickened at this stage hippocampal sulcus Fig. 24 A, B. A modification of Martin’s original figure illustrating the manner of growth of the corpus callosum with the expanding hemispheres and fibers extending between R and L hemispheres as described by Martin. corpus callosum A corpus callosum septum pellucidum developing thalamus B Hippocampus, fornix. The choroid fissure is the external sulcus that results from the infolding of the thin ventricular wall that becomes the choroid plexus. The hippocampal sulcus results from the infolding of the normal-thickness cerebral cortex in the posteroventromedial hemisphere, the part that will develop into a portion of the temporal lobe. Fig. 25. Martin’s figure. Cross-section of hemisphere at the level of the thalamus. From Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. hippocampal sulcus choroid fissure Fig. 36. Martin’s figure, modified. From Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. choroid plexus of 3rd ventricle choroid fissure hippocampal sulcus Fig. 37. Martin’s figure, modified to show the developing corpus callosum and interthalamic adhesion. From Lehrbuch der Anatomie der Haustiere, Paul Martin, 1912: Schickhardt & Ebner, Stuttgart. corpus callosum choroid plexus, 3rd Ventricle interventricular foramen lamina terminalis 3rd ventricle Interthalamic adhesion (developing) The hippocampus is formed in the posteroventromedial part of the hemisphere, the part that overlies the thalamus and midbrain. The union of the hemispheres with the diencephalon (diencephalon = epithalamus, metathalamus, thalamus, subthalamus, and hypothalamus) is wedge-shaped. Fig. 28. Dorsal view of an early stage of hemisphere development from the anterior neural tube. The oblique lines (marked by black arrows) mark the junction of the hemispheres (telencephalon) with the diencephalon. Interventricular foramen, yellow double-arrow. But a dorsal view of the developed brain looks like this: Fig. 29. Dorsal view of the canine brain. If the dorsal part of the hemispheres is cut away to expose their union with the diencephalon, it looks like this in dorsal view: Fig. 30. Union of the hemisphere with the diencephalon (indicated by black arrows), dog. Interventricular foramen, yellow double-arrow. All of the diencephalon and that part of the midbrain (mesencephalon) that is not covered by the anterior cerebellum lie chiefly ventral to the posteroventromedial part of the hemisphere. This is shown in the following views: Fig. 31. Medial view of canine brain with left hemisphere removed at its union with the diencephalon. I Fig. 32. Lateral view of canine brain with parts hidden by the hemisphere indicated. The infolded choroid plexus and hippocampal cortex look like this in cross-section (semi-diagrammatic, at the level of the tail of the caudate nucleus): corpus callosum lateral ventricle hippocampus caudate nucleus, tail stria terminalis choroid fissure hippocampal sulcus THALAMUS midline Fig. 33. Rostral view of cross-section of right hemisphere at the level of the lateral ventricle. The drawing of the hippocampus (dog) is taken from Lehrbuch der Histologie und Vergleichenden Mikroskopischen Anatomie der Haustiere, Krölling, O. and Grau, H.: 1960, Verlag Paul Parey. The pyramidal cells of the hippocampus give rise to axons that, myelinated, pass upon the ventricular surface where they form a thin white coat, the alveus. The alveus is separated from the cavity of the ventricle only by the ependyma (layer of ependymal cells). These fibers incline laterally to the margin of the choroid fissure where they gather as a large bundle, the fimbria. The fimbriae of the two hemispheres pass dorsally and rostromedially. Reaching the midline, the fiber-bundles are in apposition, ventral to the fibers of the corpus callosum where they are joined to each other and to the callosal fibers only by glia (neuroglial cells). The bundles join at the midline only briefly, their apposition forming the body of the fornix. Continuing forward, the fiber-bundles again begin to separate at the level of the lamina terminalis, dorsal to the rostral (anterior) commissure. The separating bundles, as the columns of the fornix, pass ventrally caudal to, and rostral to, the anterior commissure. The largest part, which is the part that passes caudal to the anterior commissure, continues caudally in the grey matter of the wall of either side of the third ventricle. These right and left columns of the fornix dispatch fibers to nuclei of the hypothalamus and its mammillary bodies. Fig. 34. The origin of the fiber-bundle designated the fimbria. alveus pyramidal cells fimbria stria Note that the choroid plexus, part of the original wall of the neural tube, extends from the lateral margin of the fimbria to the stria terminalis. body of fornix crus of fornix Terminology of the fornix: hippocampal commissure Fig. 35. Fimbriae and fornix. column of fornix fimbria mammillary body Note: This drawing appears to be one of Frank Netter’s. I took it from an internet site of fornix images. No indication of the artist was given. Fig. 36. Canine brain, dorsal view with corpus callosum removed, revealing the floor of the lateral ventricles. The larger figure has the hippocampal part of the hemisphere and much of the fornix removed on the left side. The roof of the third and fourth ventricles, and the cerebellum, are removed. The thalamus and brainstem are exposed. R, L hippocampus hippocampus R, L choroid plexus R, L caudate nucleus hippocampus fimbria choroid plexus of lateral ventricle body of fornix, left part cut away crus of fornix Interventricular foramen (yellow) caudate nucleus grey matter of septum pellucidum (septal nuclei) Fig. 37. Median section, canine brain. The dots indicate the course of the R column of the fornix in its caudal path deep to the wall of the 3rd ventricle. septum pellucidum and septal grey (nuclei) hippocampal commissural fibers corpus callosum R, L fimbria column of fornix body of fornix anterior commissure mammillary body Fig. 38. Cross-section through the brain of a sheep at the level of the third ventricle. The columns of the fornix can be seen deep to the wall of the third ventricle. Hematoxylin stain. Fig. 39. Brain (canine), lateral view with the position of the hippocampus superimposed. This figure also gives the approximate position of the caudate nucleus, amygdaloid body (amygdala), and corpus striatum (lentiform nucleus and globus pallidus). The stria terminalis, which is a narrow bundle of fibers arising chiefly from the amygdala and arching dorsally and rostrally alongside, and medial to, the tail and body of the caudate nucleus, is not shown here. Like the lamina terminalis, its position indicates a boundary, in this case between the thalamus and the hemisphere. caudate nucleus body tail hippocampus fimbria corpus striatum amygdala caudate nucleus tail, body, head interventricular foramen (yellow) stria terminalis 3rd ventricle thalamus lateral geniculate body telae choroideae (attachments), choroid plexus of 3rdventricle pineal body medial geniculate body thalamus Fig. 40. Dorsal view of the left caudate nucleus, stria terminalis and thalamus of the dog. This presentation has mainly considered how important features of the forebrain, telencephalon and diencephalon, are derived from the primitive neural tube. The cerebrum is generally defined as the cerebral hemispheres and the diencephalon (thalamus, and epi-, meta-, sub-, and hypo-thalamus). The mesencephalon is sometimes included. The cerebral cortex is the seat of consciousness and functions of memory, learning, behavior, and attention all take place there. The cerebral cortex is also the site of initiation of voluntary, deliberate, motor activity. We think of sensations being appreciated and associated/integrated in the cerebral cortex to provide the animal’s response. By way of a limited and somewhat simplified (but valid) example, the horse hears, sees, and smells its owner bringing hay and, owing to what the horse has learned from previous experience and the animal’s memory of it, responds to this input often by a deliberative movement of its body and a characteristic sound (“whinny”). Some visceral sensations are also being received and may modify the animal’s behavior. All involving important cortical functions. Hippocampal connections and function in humans. The hippocampus is an infolded part of the cerebral cortex. Myelinated axons from the hippocampal pyramidal neurons pass by way of the fimbria and fornix to the septal nuclei, to the hypothalamus, and to the mammillary bodies. Some fibers also pass in a reverse direction. In humans, and some of these ideas have originated in animal experimentation, the hippocampus is thought to have a prominent effect on memory and is presently subject to a considerable research owing chiefly to the interest in Alzheimer’s disease. In our domestic animals this part of the brain has also been studied owing to its cytological examination in the diagnosis of rabies in which there are present Negri bodies, eospinophilic inclusions in the cytoplasm of hippocampal neurons. Stria terminalis connections and function in humans. The amygdaloid body is a very large collection of neurons, a nucleus, that is responsible for the prominence of the rostroventral part of the piriform lobe; it is close to, and has connection with, the ventral extremity of the hippocampus. The stria terminalis is a collection of fibers (myelinated axons) arising from amydaloid neurons. The stria passes to the area of the interventricular foramen from which its branches pass chiefly to the septal nuclei, the thalamus, and hypothalamus. There are also fibers passing from these areas to the amygdaloid body. In humans, the stria is thought to mediate certain behavioral and emotional effects. Hippocampal and strial function in animals. Other than for those observations in animal experiments, and the effect of hippocampal disease in rabies, the writer knows of no specific function for these structures in animals. These structures are a part of the areas of the hemisphere associated with the olfactory sense. All of the mammals that we study are macrosmatic, having an elaborate sense of smell. The animal uses this sense to obtain food, to protect itself, to find a mate for reproduction. It is probably the most important sense for these animals and has undoubtedly wide effect on their behavior. The hypothalamus is a part of the brain from which prominent autonomic pathways proceed. These are pathways involved in regulating heart rate, blood pressure, body temperature, thirst, and the desire for food or abstinence from eating. In this respect, the association of the sense of smell with the hypothalamus makes sense even if it does not now allow us an entirely satisfying, complete. explanation.