Tag Archives: neurology

The Striatum

The striatum is the largest collection of neurons in the basal ganglia. Composed of the caudate nucleus and putamen, the basal ganglia, as the name suggests, sits at the base of the cerebrum. It receives input from regions of the cerebral cortex, the limbic system, and the sensorimotor and motivational systems via the thalamus. In addition to the cerebrum, the striatum receives input from the brainstem including the substantia nigra and the raphe nuclei of the reticular formation. The dopamine and serotonin of these two structures serve a modulatory function. Anatomists organise the striatum on the “basis of differential connectivity and distribution of neurochemical markers” (Redgrave, 2007). Processing strong excitatory input, the striatal neural circuits generate a strong inhibitory output, which controls the output of basal ganglia further along in the motor loop.

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The major cytology of the striatum is GABAergic medium spiny neurons (MSN), making up about 95% of the total cellular structure. MSNs are organised into two groups based on the peptide they contain, substance P and enkephalin and the proportion of dopamine receptors (D1 or D2) they contain. MSNs create dense networks of axon collaterals. As projection neurons, the MSNs create this dense network by forming axon collaterals with one another. Tunstall et al, 2002 found that almost 30% form an axon collateral with a neighbouring MSN. Research has shown that the function of these collaterals is in cellular recognition and “classification of cortical patterns” (Blomeley, et al. , 2009).

The striatum is a vital part of the basal ganglia, and all pathways run through it. From the striatum onwards, the pathway either becomes direct or indirect. As shown in the figure below.

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Citations:

Blomeley, C. P., Kehoe, L. A., & Bracci, E. (2009). Substance P mediates excitatory interactions between striatal projection neurons. The Journal of Neuroscience29(15), 4953-4963.

Redgrave, P. (2007). Basal ganglia. Scholarpedia, 2(6): 1825.

Basal Ganglia: Substance P

As mentioned in my last post on basal ganglia, the majority of the striatum consists of medium spiny neurons. These medium spiny neurons are GABAergic and organised based on the peptide they contain as well the dopamine receptors they contain. One these peptides is called substance P (SP). As a neuropeptide, SP functions as a neurotransmitter as well as a neuromodulator. Other than GABA, SP functions as a neurotransmitter in MSNs. Specifically, SP-releasing neurons mediate “synaptic communication between MSNs” (Blomeley, et al. , 2009).

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Previously it was thought that striatal projection neurons like MSNs only inhibit each other; however, a study by Blomeley, et al. , 2009 has proven that they can also interact in an excitatory manner. Studies have shown the synaptic NK1 receptors, whose major receptor molecule is SP are present in a glutamteric terminals in the stiratum (Jakab et al., 1996). In the study by Blomeley, the importance of these NK1 receptors was investigated. The results suggest that SP plays a crucial role in facilitating the release of glutamate between medium spiny neurons. In other words, communication between the neurons is increased by SP attaching NK1 receptors found on the terminals of glutamate releasing MSNs.

Citations:

Blomeley, C. P., Kehoe, L. A., & Bracci, E. (2009). Substance P mediates excitatory interactions between striatal projection neurons. The Journal of Neuroscience29(15), 4953-4963.

Basal Ganglia Disorders: Parkinson’s and Huntington’s Disease

My last post was exclusively about basal ganglia and the reason for this was to help clarify the parts of the brain directly involved in two very infamous disorders: Parkinson’s and Huntington’s Disease.

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Parkinson’s Disease

Parkinson’s disease is far more recognized that Huntington’s disease; however, thanks to the character Thirteen on the tv show House that might be changing. Parkinson’s disease effects about 1% of all people over the age of 50; however, as you can see from the video posted below, this is not always the case. Another example is actor Michael J. Fox, who was diagnosed with Parkinson’s at the age of 30. He has since become an activist for the cure of Parkinson’s, which led him to found the Michael J. Fox Foundation. It is not that uncommon to know someone with the disease. Many people can in fact recognize it based on the very characteristic tremors.

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Parkinson’s is classified by hypokinesia. The symptoms of Parkinson’s include slowness of movement or bradykinesiadifficulty in initiating ‘willed’ movements or akinesia, increases muscle tone or rigidity, and of course, tremors in the hands and jaws even at rest. Many  of those who suffer from the disease will eventually show signs of cognitive decline. More specifically, the substantia nigra’s input to the striatum. This input features the neurotransmitter dopamine, which facilitates the activity of the motor loop by activating cells in the putamen. As noted in the previous post, the putamen forms an inhibitory connection with neurons in the globus pallidus, which then forms an inhibitory connection with the thalamus (VLo). Due to the depletion of dopamine, the ‘funnel’ between VLo and the supplementary motor area (SMA) closes. As a result, the victim of Parkinson’s will have impaired motor function with symptoms such as ones listed above.

Treatment Options for Parkinson’s Disease

Even through Parkinson’s cannot be cured, therapies do exist to try to ease or deter the symptoms. Most therapies aim at enhancing the levels of dopamine delivered to the caudate nucleus and the putamen. The most common type of medication is known as L-dopa, which is a precursor for dopamine. This means that it participates the chemical reaction that produces dopamine. This treatment does alleviate some of the symptoms; however, it cannot do anything to stop the progressive course of the disease, nor slow the rate of cell degeneration in the substantia nigra. Currently, experiments are being conducted to test whether graftng non-neural cells, manipulated to produce dopamine, into the basal ganglia can help. Also, stem cell research shows promise to one day provide an effective treatment as well.

Huntington’s Disease

Whereas Parkinson’s is characterized by hypokinesia, Huntington’s is characterized by hyperkinesia or excessive movement. As tragic as Parkinson’s disease is, Huntington’s does seem far more frightening. A hereditary, progressive and always fatal disorder, Huntington’s  symptoms include dyskinesia or abnormal movements, dementia and disorder of the personality. The scariest part of the disorder is that the symptoms do not appear until adulthood, so unless the person knows that they have a history of the disorder, they can easily pass on the genes of Huntington’s to their children without even knowing that they have it. Genetic tests can be performed to find out for sure, but for many people it is too late at that point. The name Huntington’s comes from the abnormal gene carried by the patient. The first and most notable sign of the disease is known chorea: spontaneous, uncontrollable movements with rapid, irregular flow resulting a flicking movement in various parts of the body. In fact, Huntington’s disease can also be called Huntington’s Chorea. The devastating effects of the disease is due to the profound neuron loss in caudate nucleus, putamen and globus pallidus as well as cell loss in any other part of the cerebral cortex. The fact that Huntington’s can strike any part of the brain means that many patients suffer a variety of different symptoms, sometimes making it difficult to diagnose without a genetic test. Damage to the basal ganglia results in a loss of inhibitory output to the thalamus (VLo) resulting in the abnormal movements.

brainslice3Unfortunately, due to the progressive nature of the disorder and the genetic component, treatment for Huntington’s is virtually non-existent. Most patients with the disorder have their symptoms treated with various medications ranging from anti-depressants to sedatives and anti-psychotics.

 

Mental Retardation and Dendritic Spines

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Dendrite is Greek for “tree-like” and to explain what they do in the simplest terms possible, they receive electrochemical signals from other neurons and then pass these signal down to the soma or neural cell body. Dendrites play a critical role in determining the frequency of the action potential, which drives the electrical signal down axons of the body of the neuron towards the axon terminals. Dendrites are so essential that their architecture is a great indicator of the complexity of our neural connections. In fact, our brain function depends on strong synaptic connections, connections which are cultivated during infancy and early childhood.

Unfortunately, as with all things complex, sometimes something goes wrong in the developing process. Mental retardation occurs when there is a disruption in this early refinement of dendrites that results in cognitive impairment severe enough to disrupt adaptive behaviour. There is a wide array of genetic disorders and poor environmental conditions that can result in mental retardation. For example, Down Syndrome and PKU (both genetic disorders), accidents during pregnancy and childbirth, maternal infections with rubella, Fetal Alcohol Syndrome and environmental impoverishment. Poor environmental conditions in young children such as poor nutrition, isolation and neglect can even result in brain damage severe enough to cause damage to these sensitive dendrites.

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Healthy dendrites have spines that look like small balloons that hang of the dendrite. In cases of mental retardation dendritic spines are very thin and long, resembling the dendritic spines of a fetus. This is clearly seen in the top most image, a) and c) are healthy dendrites. This clear difference reflects the failure of normal circuits in the brain’s development. Studies by Marin-Padilla and Purpura have discovered a correlation between extent of dendritic spine damage and degree of mental retardation.

Citations:

Bear, Mark F., Barry W. Connors, and Michael Paradiso. “Neurons and Glia.”Neuroscience: Exploring the Brain. Baltimore, MD: Lippincott Williams & Wilkins, 2006. 43. Print.

Images courtesy of google images.

 

The Cranial Nerves

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The majority of the cranial nerves emerge from the brain stem on the ventral surface of the brain. Cranial nerves I and II emerge from the forebrain and cranial nerve XI from the brain stem as well as the spinal cord. As they are nerves they are classified as part of the peripheral nervous system; however, two of the cranial nerves are also considered part of the central nervous system, I and II. Each nerve often has fibers performing many different functions. Also they have associated cranial nerve nuclei in the midbrain, pons and medulla of the brainstem.

I. Olfactory: a special sensory cranial nerve responsible for our sensation of smell.

II. Optic: a special sensory cranial nerve responsible for our sensation of vision.

III. Oculomotor: a somatic and visceral motor cranial nerve responsible for the movement of the eye and eyelid as well as the parasympathetic control of pupil size.

IV. Trochlear: a somatic motor cranial nerve responsible for the movements of the eye.

V. Trigeminal: a somatic sensory and motor cranial nerve responsible for the sensation of touch on the face and the muscles of mastication.

VI. Abducens: a somatic motor cranial neuron responsible for the movements of eye.

VII. Facial: a somatic and special sensory cranial neuron responsible for the movement of muscles of facial expressions as well as the sensation of taste in the anterior 2/3 of the tongue.

VIII. Auditory-vestibular: a special sensory motor neuron responsible for the sensation of hearing and balance.

IX. Glossopharyngeal: a somatic and visceral motor cranial neuron as well as a visceral and special sensory cranial neuron responsible for the movement of muscles in the throat and the parasympathetic control of salivary glands in addition to the detection of blood pressure changes in aorta and the sensation of taste in posterior one third of tongue.

X. Vagus: a visceral motor and sensory cranial neuron as well as a somatic motor neuron responsible for the parasympathetic control of heart, lungs and abdominal organs as well as the sensation of pain associated with the viscera and movement of muscles in the throat.

XI. Spinal accessory: somatic motor neuron responsible for the movement of muscles in the throat and neck.

XII. Hypoglossal: a somatic motor cranial neuron responsible for the movement of the tongue.

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Citation:

Bear, Mark F., Barry W. Connors, and Michael A. Paradiso. Neuroscience: Exploring the Brain. Philadelphia, PA: Lippincott Williams & Wilkins, 2007. Print.

Bipolar Disorder

My most recent post showcased the artist Isti Kaldor who has bipolar disorder. This post will explain the basics of the disorder. Quite a few celebrities have come forward stating they have bipolar disorder including Catherine Zeta Jones, Demi Lovato and Stephen Fry. If you want to know the true scope, there is a wikipedia page dedicated to celebrities known to have it. Despite their very public work lives, with our limited insight into their personal lives it is difficult to really know much about the disorder. Stephen Fry, however, did a brilliant documentary on his experiences dealing with his bipolar disorder called Stephen Fry: The Secret Life of the Manic Depressive, which is available in full on YouTube.

Symptoms and Types 

As the title says, bipolar disorder is sometimes also called manic depression, but bipolar disorder is its official name. Characterised as a recurrent mood disorder, it consists of repeated episodes of mania interchanged with episodes of depression. The depressive episodes include similar but less severe symptoms of major depression such as changes in appetite, insomnia or hypersomnia, fatigue, feelings of worthlessness, guilt, inability to concentrate and suicidal thoughts. As such, the symptoms can be managed with anti-depressants. The manic periods, however, are the opposite in some respects. Symptoms consist of grandiosity, decreased need for sleep, talkativeness, flight of ideas, short attention span, and impaired judgement. It is believed that the correlation between bipolar disorder and celebrities is that those with the disorder usually experience these manic highs with bursts of creativity and inspiration. Unfortunately, the manic period can also result in promiscuity and complete loss of inhibition much like the effects of alcohol. As with any disorder, the range and complexity of symptoms varies greatly from person to person.

Bipolar comes in two general forms: type I and type II. Type I is marked by manic episodes (with or without incidents of major depression), and occurs in about 1% of the population, equally among men and women. Type II is marked by hypomania (milder form of mania that is not associated with marked impairments in judgment of performance) and is always followed by milder depressive periods.

Aetiology 

Numerous twin studies and most notably the one conducted by McGuffin and colleagues (2003) have shown that there is a high concordance between monozygotic twins with “67% MZ vs. 19% DZ.” Also, even though there is a high correlation with depression and mania, the manic component appears to be significantly more heritable in monozygotic twins. We do know that bipolar disorder affects our neurochemical pathways as treatment of lithium and anti-depressants do help alleviate the drastic mood swings. However, the actual structural component is yet to be properly determined. Studies by Bearden et al., 2001 admit that even though “dysfunction is implicated in bipolar illness patients supported by reports of relatively greater impairment in visuospatial functioning, lateralization abnormalities, and mania secondary to RH lesions” there is still not enough conclusive evidence to draw a clear link between right hemisphere dysfunction and bipolar disorder.

Strakowski et al., 2005 on the other hand using MRIs have found compelling examples of damage to the prefrontal cortical areas, striatum and amygdala that predates that onset of symptoms, which suggests that abnormal brain structure could in fact play a quintessential role in onset of the disease. Furthermore, if further studies can confirm these findings, it could offer psychiatrists and neurologists a revolutionary way of pre-symptomatic diagnosis. As of 2012, Strakowski et al. have reached a “general consensus” that bipolar type I occurs due to abnormalities within networks that control emotional behaviour such as the prefrontal cortex and limbic area, specifically the amygdala.

Treatment 

To date the most effective treatments for bipolar disorder include lithium (used to target the manic episodes), anti-depressants such as SSRIs, monoamine oxidase and tricyclics. Other types of medication such as anti-anxieties and anti-psychotics are used in some cases depending on the severity of the symptoms. In addition to medication, therapy has also been proved to significantly reduce the psychological stress of the disorder.

Citations:

Bear, Mark F., Barry W. Connors, and Michael Paradiso. Neuroscience: Exploring the Brain. Baltimore, MD: Lippincott Williams & Wilkins, 2006. Print.

Bearden, C. E., Hoffman, K. M. and Cannon, T. D. (2001), The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disorders, 3: 106–150. doi: 10.1034/j.1399-5618.2001.030302.x

Malliaris, Yanni,. “1.7 Aetiology of Bipolar Disorder.” 1.7 Aetiology of Bipolar Disorder. BipolarLab.com, 20 Aug. 2010. Web. 03 Aug. 2013.

Strakowski, S. M., Adler, C. M., Almeida, J., Altshuler, L. L., Blumberg, H. P., Chang, K. D., DelBello, M. P., Frangou, S., McIntosh, A., Phillips, M. L., Sussman, J. E. and Townsend, J. D. (2012), The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disorders, 14: 313–325. doi: 10.1111/j.1399-5618.2012.01022.x