Lab 7: Limbic System & Cerebral Cortex

Lab Summary

This laboratory will deal with a number of areas that are concerned with more complex functions of the nervous system. These include 

SECTION 1: Limbic System 

SECTION 2: Hypothalamus 

SECTION 3: Thalamo-cortical Connections 

SECTION 4: Organization of the Internal Capsule 

SECTION 5: Neocortex

Limbic System

Objectives


  1. The Limbic system has multiple roles in behavior. Identify the major structures and pattern of connectivity associated with the memory (hippocampus, fornix, hypothalamic and thalamic nuclei, the cingulate and entorhinal cortical areas) and emotional (hippocampus, fornix, amygdala, septal nuclei, habenula, hypothalamus and midbrain tegmentum) circuitry of the Limbic system.

On the whole brains (Figure 7.1), locate these regions of the limbic system: 

Primary Olfactory cortex includes the piriform cortex and the periamygdaloid cortex. 

Anterior commissure contains two sets of axons. 1) axons from anterior olfactory nucleus to contralateral bulb and contralateral anterior olfactory nucleus, and 2) axons connecting areas of the two temporal lobes. 

Parahippocampal gyrusmedial and basal region of the temporal lobe, bordered laterally by the collateral sulcus. This cortical area contains the entorhinal and perirhinal cortical regions and is a major input and output relay region between the hippocampus and areas of association cortex. These structures play an important role in memory and emotion as part of the Limbic circuitry of the brain. 

Uncusis a surface landmark rostral and medial to the parahippocampal gyrus. Deep within the uncus lies the amygdala. 

Entorhinal area small posterior part of lateral olfactory gyrus plus parahippocampal gyrus. 

Hippocampal sulcus follow the parahippocampal gyrus to its medial edge. Deep within this sulcus lie the hippocampus and the dentate gyrus

On the half brains or brain stem preparations (Figure 7.2A-B) locate: 

Figure 7.2 Sagittal Brain 

Lamina terminalisrostral border of third ventricle, between anterior commissure and optic chiasm. This is the region of anterior neural tube closure in the embryo. 

Cingulate gyrus on the medial surface follow this gyrus from the caudal area of the parahippocampal gyrus over the corpus callosum. 

Fornix – In the brain stem preparation follow the fornix rostrally from the inferior horn of the lateral ventricle. The fornix consists of axons from the hippocampus that arch over the thalamus and terminate in the mammilary bodies and the septal region. Axons traveling from the medial septal nuclei to the hippocampal formation are also found in the fornix. Try to gain a spatial understanding of the fornix, hippocampus and amygdala in the cerebral hemispheres using AR Brain  

Mammilary bodies – receive input via the fornix and project to anterior thalamic nuclei via mammilo-thalamic tracts. 

Anterior nucleus of thalamus locate the anterior tubercle on the brain stem preparation. The anterior n. projects to the cingulate gyrus. Trace one of the major limbic pathways, for example, the Papez circuit (Figure 7.3A-C)

Septal region – located immediately rostral to the hypothalamus and superior to the anterior perforated area. Nuclei of the medial septal region provide cholinergic input to the “hippocampus and may be active in modulating memory functions. The lateral septal region receives input from the hippocampus and projects to the medial septal nucleus providing a feedback loop important to memory formation. Locate the septal region on the medial surface of the brain. 

Stria terminalisaxons from the amygdala passing in the n. stria terminalis to the septal nuclei and hypothalamus that are important in autonomic functions and emotion. Follow as a thin line on the surface of the caudate- thalamic border. 

Stria medullaris – consists of axons from the septal nuclei, the hypothalamus (preoptic region), and the anterior nucleus of the thalamus that project to the habenula. 

Habenula – visible as small bands just rostral to pineal gland on the dorsal surface of the third ventricle. The habenula projects via the fasciculus retroflexus to the interpeduncular nucleus and this is a visceral efferent pathway from the limbic system to the rostral areas of the midbrain. 

Papez circuit

Hippocampus ⟶ Mammillary Body ⟶ Anterior N. ⟶ Cingulate Gyrus ⟶ Hippocampus

Limbic-Habenular Pathway

Hippocampus, Amygdala ⟶ Septal nuclei, Hypothalamus, Anterior N. ⟶ Habenula ⟶ Interpeduncular N. ⟶ Midbrain

Use the Coronal Weigert (fiber stain) Series to identify many of the above structures in section (Figure 7.4). 

During the laboratory, cell stained sections through a human hippocampus will be available. Use Figure 7.5 to distinguish the three cell layers of the hippocampus and of the dentate gyrus. Which cells give rise to the axons of the fornix? Review the infolding of the brain surface that led to the formation of the hippocampus. 

Now use the Horizontal Weigert (fiber stain) Series to examine the progression of these structures (Figure 7.5): 

Hypothalamus

Objectives


  1. The hypothalamus integrates many functions and exerts control through the endocrine, autonomic, somatic, and hypophyseal systems. Identify the major subdivisions of the hypothalamus and their role in emotion and homeostatic functions.

Return to the base of the whole brain (Figure 7.6A); review the surface landmarks of the hypothalamus. These are used to subdivide the hypothalamus into regions (Figure 7.7C):  

  • preoptic (rostral to the optic chiasm) 
  • supraoptic (above the chiasm)
  • tuberal (above the hypophysis)  
  • mammilary regions

On the medial surface of the sagittal half brain (Figure 7.6B & C), trace the borders of the hypothalamus, and locate the supraoptic recess and the infundibular recess of the third ventricle. 

Figure 7.6 Hypothalamus

In addition to regional division of the hypothalamus in the anterior to posterior dimension, the hypothalamic nuclei are als divided into lateral and medial nuclear groups. The division between medial and lateral is roughly demarcated by the position of the fornix. The medial nuclei are more distinct and have names at each level (Figure 7.7).

Figure 7.7 Hypothalamic Nuclei

Look at the Coronal Weigert Series file (Figure 7.8) to see relations of the hypothalamic nuclei. Individual nuclei are not distinguishable in the slides. Using the Nissl stained sections of the monkey brain in your slide collection try to visualize the various hypothalamic nuclei and the hypothalamic divisions using Slides 9 through 19 in your slide box (these numbers may vary slightly for each set).

Thalamo-cortical Connections

Objectives


  1. Identify the relay sensory nuclei of the thalamus for visual, auditory and somatosensory function, as well as the nuclei relaying motor information to the cortex. Describe the inputs and cortical output targets of these nuclei.

Most of the thalamic nuclei project to the cortex. However, as an exception, the centromedian nucleus receives major afferents from the striatum and motor cortex and projects back to the caudate-putamen. The remaining intralaminar thalamic nuclei appear to have diffuse, widespread projections to the cortex (Figure 7.9). Cortical projections of the other thalamic nuclei are more restricted. 

Motor Areas: Using the whole brain, locate the central sulcus, the precentral gyrus, the postcentral gyrus, and the paracentral lobule (found on the medial surface). Recall the location of the primary motor area (area 4). What thalamic nucleus projects to this region? Anterior to area 4, locate area 6, the premotor area, and area 8, the frontal eye fields (the cortical region that controls conjugate eye movements). What is the thalamic projection to area 6? 

Figure 7.10 Thalamic-subcortical projections

Sensory Areas: In the parietal lobe, locate the primary somatosensory cortex along the postcentral gyrus. Note that the primary motor and somatosensory areas extend along the walls of the gyri, deep into the central sulcus, as well as superficially. Name two thalamic nuclei that project to areas 3, 1 and 2. Locate the parieto-occipital sulcus (easy to find on the medial surface). The occipital pole contains the primary and secondary visual areas; these will be studied in more detail during the sensory lab; what thalamic nucleus projects to the primary visual cortex? The auditory cortex is located along part of the border of the superior temporal gyrus, and receives afferents from the medial geniculate nucleus. 

Association Areas: Superior to the lateral sulcus, on the lateral surface of the parietal lobe is an area of sensory association cortex that receives projections from the pulvinar

Limbic Areas: Cortical limbic regions receiving projections from thalamic nuclei are the cingulate gyrus with input from the anterior nucleus, and the prefrontal cortex with input from the mediodorsal nucleus. The interrelationships of these regions will be discussed in the limbic labs and lectures. 

Note that there are also many projections between the thalamus and subcortical areas of the brain (Figure 7.10). 

Finally, review the projections from each of the thalamic nuclei listed in Table 7.1. 

Table 7.1 Thalamic Projections
NucleusClass of AfferentsSource of AfferentsEfferent Target(s)
VPLSensoryMedial lemniscus,
lat. spinothalamic
Primary somatosensory cortex
VPMSensoryVentral trigeminothalamic tractPrimary somatosensory cortex
LGNSensoryOptic tractPrimary visual cortex
MGNSensoryInferior colliculusPrimary auditory cortex
VAMotorGlobus pallidus internalPre-motor cortex
VLMotorDeep cerebellar nucleiPrimary motor cortex
ALimbicMammillary bodiesCingulate gyrus
MDmLimbicHypothalamus,
septal areas,
amygdala
Ventral medial pre-frontal cortex
MDpAssociationalSubstantia nigra pars reticulataDorsal lateral pre-frontal cortex
PulAssociationalSuperior colliculusAssociational cortices of parietal, temporal, and occipital lobe
CMDiffuseGlobus pallidus internalPutamen and motor cortex

Organization of the Internal Capsule

Objectives


  1. Describe the functional organization of the internal capsule and identify the vascular supply to the internal capsule and thalamus. 

The internal capsule contains all efferents and afferents projecting between the cortex and the more caudal structures of the brain. On horizontal sections locate the anterior limb (between the lenticular and caudate n.), the genu, the posterior limb (between the lenticular n. and the thalamus) and the retrolenticular region (behind the lenticular n.) (Figure 7.11). What important sensory radiation is found in the superior thalamic radiation? – in the posterior? – in the inferior?

Figure 7.11 Organization of ascending and descending information flowing through the internal capsule.

Blood Supply of the Thalamus and Internal Capsule

Review Figure 7.12A-B illustrating the blood supply to the thalamus and to the internal capsule. Damage to which artery will have the most profound effect on corticospinal transmission for the body?

Figure 7.12 Blood supply to internal structures

Use Table 7.2 to review the features of the internal capsule. 

Finally, for review, use the coronal, sagittal and horizontal tabulas to once again follow the transition of the thalamic nuclei and their relationships with other structures, i.e. basal ganglia, corpus callosum, ventricles, etc., that you have studied. Thalamic projections: test yourself by clicking on the boxes. 

Table 7.2 Organization of the Internal Capsule

Ascending Projections

ProjectionsAnt. Limb, Post. Limb, or GenuConnectsBlood Supply
Ant. Thal. Rad.AnteriorMedial and anterior thalamus to frontal lobeMedial striate from ant. cerebral artery
Sup. Thal. Rad.PosteriorSomatosensory relay (VPM and VPL to primary somatosensory cortex)Lateral striate
Post. Thal. Rad.PosteriorVisual relay (LGN to primary visual cortex)Anterior Choroidal
Inf. Thal. Rad.PosteriorAuditory relay (MGN to primary auditory cortex)Anterior Choroidal

Descending Projections

ConrticopontineAnteriorFrontal cortex to pontine nucleiMedial striate, lateral striate
ConrticopontinePosteriorParietal occipital, and temporal cortex to pontine nucleiLateral striate, anterior choroidal
CorticonuclearGenuMotor cortex to cranial nerve motor nucleiInternal carotid, lateral striate
CorticoreticularGenuPremotor and supplementary motor to pontine and medullary reticular nucleiInternal carotid, lateral striate
CorticospinalPosteriorPrimary motor cortex, premotor cortex, and somatosensory cortex to spinal cordLateral striate, anterior choroidal

Neocortex

Objectives


Areas of the neocortex are important for complex processing of sensory information and execution of integrated motor output: 

  1. Distinguish between primary sensory, primary motor and association areas of the cerebral cortex based upon the thickness and cellular features of the six cortical lamina. 
  2. Identify the blood supply of the cerebral hemispheres and be able to discuss the impact of compromise of these vascular elements on sensation, motor activity and behavior. 

The olfactory cortex and parts of the limbic cortex (hippocampus, dentate gyrus, and part of the parahippocampal gyrus), consist of three layers, and represent the oldest cortex. The rest of the cortex, or neocortex, consists of 6 cell layers. In humans much of the six layered cortex is devoted to association cortical areas, with less area devoted to specific motor and sensory areas. The cortex is not uniform in structure, and cortical areas differ on many factors, including overall thickness, the size and composition of layers, the pattern of connections with other cortical or subcortical areas, etc. These cytoarchitectonic features correlate somewhat with function. From the histological and functional differences a variety of maps of the cortex have been made; the most popular is Brodmann’s cytoarchitectonic map (Interactive 7.1& Figure 7.13). Of particular histological importance is the recognition that primary sensory cortical areas (somesthetic, visual, and auditory) have a thin cortex with a very well developed granule cell layer. Recall the striate cortex of the visual area (Interactive 7.1); the stripe consists of axons penetrating the thick granule cell layer. In contrast, primary motor cortex has few granule cells, is thick, and has large pyramidal cells. The remaining cortical areas have a more balanced development of the six layers, but there are differences between the association cortex of the frontal, parietal, and occipital lobes. Two slides will be available for study of the layers of the cortex. One is from the central sulcus that has both primary motor cortex with large pyramidal cells, and primary sensory cortex with a dense granule cell layer. Use the difference in thickness of the two cortices to determine which is sensory and which is motor. For each, determine with the microscope the: molecular layer (I), the external granular layer (II), the external pyramidal layer (III), the internal granular layer (IV), the internal pyramidal layer (V), and the multiform or fusiform layer (VI). The other slide is from the striate cortex; try to find the six layers in this cortex and find the stripe in the internal granular layer. 

On the whole brain, distinguish primary sensory and motor areas from association areas. Particularly important areas to locate are those concerned with language (Figure 7.13 and Figure 7.14): 

Motor speech area of Broca (area 44 and 45) – found on the opercular surface of the inferior frontal gyrus. A lesion here produces motor speech aphasia, in which comprehension is intact but the speech is difficult and distorted.  

Wernicke’s area (area 22 and part of 42) – found on the superior temporal gyrus, caudal to the primary auditory areas. A lesion here produces difficulty in comprehension of language, naming of objects, and in forming of sentences (receptive aphasia). 

Inferior parietal lobe (area 39 and 40) – located on the angular and supramarginal gyri. A lesion here produces difficulties in associations between auditory, visual and tactile stimuli. Reading and writing are disturbed. 

Arcuate fasciculus – this fiber tract connects Wernicke’s and Broca’s areas. Destruction of this connection can produce conduction aphasia, in which the patients can comprehend speech and speak spontaneously, but cannot repeat or write sentences they hears. 

A summary of the functional organization of the cerebral cortex using Brodmann’s system can be found in Figure 7.14. 

Figure 7.14 Functional organization of cerebral cortex

Review the blood supply of the cerebral cortex (Figure 7.15A). Identify the arterial distribution supplying lateral areas of the cerebral cortex. What is the distribution of the middle (MCA), anterior (ACA) and posterior (PCA) cerebral arteries to internal brain regions structures in the coronal (Figure 7.15B) and horizontal (Figure 7.15C) planes of section? Start at the base of the brain and trace the anterior, middle and posterior cerebral arteries through their cortical distributions. Notice the supply of the primary motor and somato-sensory regions, particularly considering their somatotopic organization and the areas of the body that would be affected by occlusion of different arteries. 

Figure 7.15 Blood Supply