Basal nuclei

Around the central core of the brain are a number of structures that collectively make up the deep brain nuclei, which are organized into the limbic system, and the basal nuclei. These systems are closely connected to the thalamus, the hypothalamus and the sensory and motor areas of the cerebral cortex. The limbic system is concerned with emotions, behaviour and memory and the basal nuclei are concerned with control of movement, although there is overlap between the two. Malfunction of these areas is implicated in disorders such as Parkinson s disease and schizophrenia. 

There are four main neuronal systems in the brain in which dopamine is a transmitter the basal nuclei the hypothalamic-pituitary pathway and the mesolimbic and mesocortical pathways (see Figure 11.3). 

The basal nuclei are a collection of paired structures that modulate motor pathways from the cerebral cortex and play a role in the fine control of movement. Part of this is a pathway from the substantia nigra in the midbrain to an area called the striatum in the basal nuclei. The neurotransmitter of this pathway is dopamine and loss of dopamine-containing neurons here causes Parkinson s disease (see page 212). 

Many anti-psychotic drugs have what are called Parkinsonian or extra-pyramidal side effects. These are abnormalities of movement that resemble Parkinson s disease (see page 211) and are due to the blocking of dopamine D2 receptors in the basal nuclei. Anti-psychotics that also have anti-cholinergic activity (for example pericyazine) cause fewer Parkinsonian side effects. 

Parkinson s disease is a disorder of the basal nuclei in the brain. Post-mortem studies of brains from patients with Parkinson s disease have shown greatly decreased levels of dopamine in the basal nuclei. The main pathology is degeneration of the dopaminergic neurons of the pathway from the substantia nigra in the brain stem to the corpus striatum (the nigrostriatal tract). 

It can be difficult to determine onset of disease. Because compensation occurs, there must be 80% depletion of dopamine in the basal nuclei before symptoms appear. Compensation takes the form of increased activity in the remaining dopaminergic neurones and increase in numbers of receptors. 

Dopamine pathways normally balance cholinergic pathways in the basal nuclei and many of the symptoms of Parkinson s disease are thought to be due to over activity of cholinergic pathways. Therapy therefore aims to improve dopaminergic transmission or inhibit cholinergic pathways to restore the balance. 

Other known toxic causes include Wilson s disease, where there is deposition of copper in the basal nuclei, and mercury and manganese poisoning. 

These act directly on dopamine receptors in the brain and are selective for the D2 subtype found in the basal nuclei. An example is bromocriptine. 

Schizophrenia is the most common psychotic disorder. It may be due to an abnormality of dopamine receptors or increased release of dopamine in particular regions of the brain, the mesolimbic and mesocortical pathways. In addition, there may be an abnormality of serotonin pathways that interact with dopamine. Most drugs effective in the treatment of schizophrenia block dopamine receptors and some of the newer ones block serotonin receptors. Adverse effects of antipsychotics can be severe and are largely due to the blocking of dopamine receptors in other parts of the brain. For example Parkinsonism and tardive dyskinesia are the result of dopamine receptor blocking in the basal nuclei. 

Parkinson s disease was the first neurological disorder to be associated with deficiency of a specific neurotransmitter. In Parkinson s disease, there is a deficiency of dopamine in the basal nuclei, which leads to overactivity of cholinergic pathways and the characteristic hypokinesia, rigidity and tremor. Drugs used to treat Parkinson s disease aim to replace dopamine stimulate dopamine receptors or the release of remaining dopamine reduce breakdown of dopamine or reduce excessive parasympathetic activity. More recently, attempts have been made to replace dopamine-secreting cells by transplantation of fetal brain tssue. 

It is important to note that the rabies virus can also be transmitted through the colonization of the olfactory bulbs via the nasal cavity (Fig. 12.4). Indeed, animal models of infection have shown that viruses could migrate from the olfactory bulb to higher brain regions, including the basal nuclei, hypothalamus, and cerebellum. " ... 

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