 Good day everybody. Welcome to our next episode of the section of the human brain. Today I'll talk about two things. I'll talk about the components of what is known as the basal forebrain and then I'm going to talk about the so-called mesolymic and mesocortical structures or the mesocortical tracts with two clinical correlations. Before that, my name is Dr. Sanjay Sanyal. I'm the professor and course director of neuroscience and the camera person is Mr. Mark Lesser. So coming to the first topic, the basal forebrain. What is this basal forebrain and what are the components? So in this we have a section of the brain here, a sagittal section. Many of these structures are visible here but some structures will not be visible but I'll mention them and I'll tell them where they are located. The first component of the basal forebrain is this structure that we see here. This is the OFPFC, the orbital frontal PFC, one which rests on the cribid form plate of ethmoid bone in the anterior cranial fossa. The second component of the basal forebrain is what is known as the septal area. The septal area itself is a composite area and includes two things. One is called the cortical areas and the other is called the sub-cortical nuclei of the septal area. So let's take a look at the cortical areas. The cortical areas are the ones which are located in this region. One portion of the cortical area is located under the corpus callosum and that is known as the sub-cortical area. It's sub-callosal area and there's another one which is located just adjacent to the lamina terminalis, this portion of the cortex. This is known as the paraterminal. So the sub-callosal and the paraterminal, these are the cortical areas of the septal area. What about the septal nuclei, the sub-cortical nuclei? This is the septum pellucidum and this is the anterior commissure. Between the septum pellucidum and the anterior commissure are a collection of nuclei which are collectively referred to as a sub-cortical septal nuclei. They are further subdivided into a medial group, a lateral group and a posterior group but we shall not go into the specifics of that. So this is the second major component of the basal forebrain, namely the septal area. The third and the fourth components are not visible because they are on either side of the midline. One of them is what is known as the ventral striatum. The ventral striatum is situated deep inside this location. It is located just ventral to the corpus striatum, namely the caudate nucleus and the putamen and this ventral striatum includes most important for us here what is known as the nucleus accumbens and I shall talk quite a bit about the nucleus accumbens in the subsequent part of my discussion and the other component of the ventral striatum is what is known as the olfactory tubercle which we shall not refer to any further. The fourth component of the basal forebrain is known as the ventral pallidum which is located just behind the anterior commissure but it is also located deep inside and therefore we cannot see in this dissection. The ventral pallidum is located just ventral to the globus pallidus and it includes what is known as the substantia inominata. In the earlier days it was not very clear what was the function that's why it was called inominata but now we know it includes a very important nucleus known as the nucleus basalis of Maynard which is rich in cholinergic neurons and is one of those prime structures which is degenerated in Alzheimer's disease but we shall not go into that any further. And the final component, the fifth component of the basal forebrain is the anterior hypothalamus which is just adjacent to the laminaterm analysis in this location here and that includes the pre-optic nucleus. We shall not mention that anymore. So the structure which we shall focus on predominantly will be the PFC, the septal area and the ventral striatum more specifically the nucleus accumbens. Okay so that's about the components of the basal forebrain. Now let's come to something else before I talk about the meso olympic and the mesocortical structures. Now if you take a look at the specimen here what we see here, this portion here, this is the hypothalamus and the upper portion this is the thalamus therefore this is the cavity of the third ventricle. Now this hypothalamus is divided into a medial portion which we can see here and a lateral portion which is further down which we cannot see and the dividing structure between these two is the hippocampus mammillary tract and the mammillothalamic tract which divides the thalamus into a medial and a lateral portion. Why am I mentioning this is because running through the lateral hypothalamus is a tract which is referred to as the medial forebrain bundle. This medial forebrain bundle gives passage to the meso olympic and the mesocortical tract. Having said that now let's come to the meso olympic and the mesocortical tract proper. Where does this tract start from? If you take a look at this specimen here this is the midbrain, this is the pons and this is the medula. So let's focus on the midbrain. This portion of the midbrain is the tegmentum of the midbrain. This whole thing is the tegmentum of the midbrain and if you look very closely here this is the region of the tegment of the midbrain which contains several nuclei clusters. They are called the reticular nuclei of the midbrain and some of these nuclei are one the ventral tegmental area VTA, the dorsal tegmental area DTA, the lateral tegmental area superior central nucleus. There are several such nuclei in this location here. So these are the reticular nuclei in the reticular formation of the midbrain. Let's focus on the ventral tegmental area the VTA which is going to be the main crux of our discussion right now. Projections start from the ventral tegmental area and they go to wide areas of the limbic system and the wide areas of the cortex and they are respectively referred to as the meso olympic and the mesocortical areas. So let's take a look at the meso olympic projections. Where does this meso olympic projection go? The meso olympic projection starts from the ventral tegmental area and it projects to at least four well-known locations. Through the medial forebrain bundle which I mentioned earlier some of the fibers they go to the region here. This is the entorhinal area, the secondary olfactory cortex. It is also part of the limbic system. This is the entorhinal area. This is blood man area 28. Another component of the meso olympic circuit goes from the ventral tegmental area also goes through the medial forebrain bundle and it goes to the amygdala which is located deep inside where my probe is. It is located on the roof on the tip of the inferior horn of the lateral ventricle. It is located deep. It is not visible here. A third component of the meso olympic tract it goes to the septal nuclei which I mentioned earlier to the septal nuclei and the fourth component of the meso olympic tract goes to the nucleus accumbens which I mentioned earlier which is located in the ventral striatum. So these are some of the important components of the meso olympic tract. Now let us take a look at the mesocortical tract. It is actually basically a continuation but it is considered separately because of its pathophysiological implications. The mesocortical tract also starts from the ventral tegmental area. It goes through the medial forebrain bundle and it goes to the prefrontal cortex. This is the medial prefrontal cortex. This is the orbital frontal prefrontal cortex. It goes to the PFC and some of the fibers they go to the anterior part of the cingulate gyrus. So this is the mesocortical tract. So in a nutshell we have the meso olympic tract going from the VTA to the amygdala to the entorhinal cortex to the septal area and to the nucleus accumbens and we have the mesocortical tract going from here to the PFC and to the cingulate gyrus. Having mentioned all these now let us come to the clinical implications of this. Let us start with the mesocortical tract. The mesocortical tract which goes from here if there is a failure of this mesocortical tract then we get what is known as the negative symptoms of schizophrenia. The failure of the mesocortical tract produces negative symptoms of schizophrenia. One thing I forgot to mention but which I am going to mention now is the ventral tegmental area the projections from the ventral tegmental area to all these structures are all dopaminergic projections. The ventral tegmental area is rich in dopamine and all its projections are dopaminergic projections. So to come back to where I was failure of dopaminergic projections from the VTA to the cortex mesocortical tract produces the negative symptoms of schizophrenia and therefore the mechanism of treating this negative symptom of schizophrenia is either to block the 5HT2 receptors if we block the 5HT2 receptors in the mesocortical tract then we allow the dopaminergic projections to continue on to the mesocortical system and alleviate the negative symptoms of schizophrenia. So that is the significance of the mesocortical tract. Now let us come to the significance of the mesolimbic tract. In the mesolimbic tract we will focus on that component of the tract which we had mentioned starts from the ventral tegmental area and goes to the nucleus accumbens. Now the nucleus accumbens has got rich number of D2 receptors dopamine 2 receptors and it needs dopaminergic projections from here and that has got plenty of clinical significance clinical implications. The first one of that is the so called pleasure reward circuit or the NAC pathway or the pleasure or the drug addiction pathway. How does this work? Normally the ventral tegmental area is under an inhibitory influence from the substantia nigra pars reticulator which is located in the anterior part of the midbrain. The substantia nigra pars reticulator releases GABA and inhibits the ventral tegmental area and therefore it prevents this from stimulating the nucleus accumbens with dopamine. However if we indulge any pleasurable activity like for example taking drugs of recreational abuse or any pleasurable activity for that matter then what happens this inhibition is disinhibited and the ventral tegmental area becomes active enough to start stimulating the nucleus accumbens with rich dopaminergic projections. Once the nucleus accumbens receives dopamine it wants it craves more and more and a vicious cycle of pleasure reward cycle is set into motion and that's what produces the drug addiction. Therefore it has been found clinically as well as experimentally that if an experimental or a clinical lesion is produced in the nucleus accumbens it goes a long way towards reducing this drug seeking behavior because the more dopamine nucleus accumbens receives the more it wants and the more it craves and that's what produces this drug dependency and the drug addiction. So this pathway from the ventral tegmental area to the nucleus accumbens this specific push component of the mesolimbic tract is also referred to as the NAC pathway NAC NAC being the short form for nucleus accumbens it is also known as the pleasure reward circuit. Now let's come to another aspect of this circuit this mesolimbic pathway from the nucleus accumbens from the ventral tegmental area to the nucleus accumbens it is normally inhibited this pathway is normally inhibited by yet one more projection and that is from the PFC this PFC normally keeps this under inhibition. So what happens is if there's a lesion of the PFC prefrontal cortex due to any any reason this prefrontal cortex cannot inhibit the mesolimbic pathway and therefore the mesolimbic pathway gets what is known as disinhibited and this disinhibition results in what is known as the positive symptoms of schizophrenia. So here we see a different situation disinhibition of the mesolimbic pathway produces positive symptoms of schizophrenia while inhibition of the mesocortical pathway which we had mentioned earlier had produced negative symptoms of schizophrenia. So let's come back to this positive symptoms of schizophrenia disinhibition of the mesolimbic tract by a lesion of the PFC produces positive symptoms schizophrenia and therefore one of the methods of treatment of the positive symptoms of schizophrenia is to stimulate is to prevent dopamine release from the ventral tegmental area to the nucleus accumbens by giving dopamine D2 blockers. So therefore that is another method of treatment of positive symptoms of schizophrenia and that is to block the nucleus accumbens dopamine D2 receptors by means of D2 blockers so that the positive symptoms of schizophrenia are relieved. So in a nutshell what we have described is we have described the basal forebrain components we have described the mesolimbic and the mesocortical tract which travels to the medial forebrain bundle we have mentioned the negative symptoms of schizophrenia caused by failure of the mesocortical pathway and we have mentioned the positive symptoms of schizophrenia caused by disinhibition of the mesolimbic pathway and the principles of treatment of each of these. Okay thank you for watching ladies and gentlemen if you have any comments or questions please put them in the comment section below have a nice day