The magnum opus
Isn't M2 JUST about memory work? You think about it
The visual pathway
An image that passes through the lens is inverted and reversed, and then projected onto the retina. The right visual hemifield is picked up by the left temporal and right nasal hemiretinas, whereas the left visual hemifield is picked up by the right temporal and left nasal hemiretinas. The retina is made up of 3 functional layers: The photoreceptors receive and transduce the light signals into action potentials, and then transmit them to the bipolar cells, which in turn transmits the signal to the ganglion cells.
There are also 2 tangential sets of cells, the horizontal and amacrine, that seek to modulate and integrate information. While the horizontal cells modulate information between the outer nuclear and bipolar cells, the amacrine cells do so for the bipolar and the ganglion.
Axons project from the ganglion cells and form optic nerves, which converge at the optic chiasma. In the chiasma, fibres carrying information from the left and right nasal hemiretinas cross each other in a hemidecussation, but the fibres from the temporal hemiretinas do not cross. Thereafter, two optic tracts fan out from the optic chiasma, each optic tract relaying information from the ipsilateral temporal hemiretina and contralateral nasal hemiretina.
The optic tract travels to the lateral geniculate nucleus. However, a minority of fibres go to these few places: The superior colliculus, which is responsible for eye movements; the suprachiasmic nucleus, responsible for circadian rhythms regulating behaviour in response to light and darkness; and the pretectal nucleus, responsible for the papillary light reflex.
The lateral geniculate nucleus sends out fibres to reach the primary visual cortex. Fibres carrying information from the superior visual field travel in Meyer’s loop, which swings around the inferior part of the lateral ventricle. Fibres carrying information from the inferior visual field travel in the parietal lobe.
From the primary visual cortex, fibres travel via the dorsal and ventral pathways. The dorsal pathway conveys spatial and temporal relationships and goes to the posterior part of the parietal lobe. The ventral pathway conveys form and colour and goes to the underside of the temporal lobe.
Phototransduction
Each photoreceptor contains an opsin molecule bound to a molecule of 11-cis retinal. At the resting state, the photoreceptor is depolarized, since the cGMP gated ion channel is open, allowing for the influx of cations. When a photon strikes the photoreceptor, 11-cis retinal photoisomerises into the trans form and changes the conformation of opsin. This activates nearby G proteins which then activate nearby phosphodiesterases, which cleave the cGMP gate. The gate closes, causing cation influx to cease, resulting in hyperpolarisation.
As a result, glutaminergic transmission from the photoreceptor ceases. The bipolar cell is thus depolarized, and subsequently passes a signal to the ganglion cell also.
There are two types of ganglion cells, the ON and OFF centre cells. ON centre cells are stimulated most when the centre of their receptive field is light and the periphery is dark. OFF centre cells, conversely, are stimulated most when the periphery is dark and the centre is illuminated.
The two types of photoreceptors, rods and cones, are different in various ways.
Rods are more sensitive than cones. Since rods contain more pigment, a single photon is sufficient to activate a rod. However, hundreds of photons are needed to activate cones.
However, cones have a higher acuity than rods. Many rods converge onto one bipolar cell and their information is thus averaged out. On the other hand, each cone converges onto a bipolar cell
Rods a achromatic, given that they have only one type of opsin. However, cones have different isomers of opsin that respond to different wavelengths of light. The proportion of the activation of the different types of cones gives rise to colour perception, according to the trichromatic theory. Thus, cones are chromatic.
Visual field losses
An incomplete lesion of the optic nerve may cause scotoma in the affected eye. However, if the optic nerve transmission is completely blocked, monocular blindness occurs.
When a pituitary adenoma impinges on the medial part of the optic chiasma, the fibres carrying information from the two nasal hemiretinas become defective. Hence, peripheral vision is lost, bitemporal hemianopias result
Optic tract lesions are rare, but when they occur, a homonymous hemianopia results, since each optic tract carries information from the ipsilateral temporal hemiretina and the contralateral nasal hemiretina. The outside of the tract is more affected than the inside and the hemianopia is reported to be incongruous
There may be a lesion of the Meyer’s loop, owing to perhaps a tumour in the temporal lobe. Vision in the superior part of the contralateral visual hemifield is lost, resulting in superior quadrantanopia. If the tumour impinges the optic radiation from above, inferior quadrantanopia occurs instead. A complete block of the optic radiation may occur due to a large tumour and homonymous hemianopia results
If blood supply in the posterior cerebral artery is impeded due to a stroke, perhaps, then there will be homonymous hemianopia with macular sparing. The macula is spared because it has a dual blood supply, from both the posterior and medial cerebral arteries.
A fall can lead to contusion in the occipital lobe, and a bilateral central scotoma results.
The basal ganglia consist of these four parts: The striatum, made up of the caudate nucleus, nucleus accumbens and putamen; the subthalamic nucleus; the globus pallidus intern and externa, with the substantia niagra pars reticulata as a midbrain extension; the subsantia niagra pars compacta.
4 loops go through the basal ganglia- they are the motor, limbic, occulomotor and cognitive loops.
The motor loop is responsible for learned movement. Its key input component is the striatum, which mainly receives stimulatory glutaminergic signals from the neocortex. The key output component is made up of the globus pallidus interna (GPi) and the substantia niagra pars reticulate (SNr). The GPi-SNr sends out an inhibitory GABAergic projection to the stimulatory cells of the thalamus, thus exerting negative feedback on the striatum.
In between the input and output lie the direct and indirect pathways. The direct pathway arises from striatal cells carrying GABA and the neuroactive peptides dynorphin and substance P. It is a monosynaptic GABAergic inhibitory projection from the striatum to the GPi SNr. The indirect pathway arises from striatal cells carrying GABA and enkephalin, and projects polysynaptically to the GPi-SNr, via the globus pallidus externa (GPe) and the subthalamic nucleus (STN). This occurs: the striatum sends out a GABAergic inhibitory projection to the GPe, which sends out a GABAergic inhibitory projection to the STN. The STN sends out a glutaminergic stimulatory projection to the GPi-SNr
The limbic loop is concerned with the expression of emotion through motion. It starts off at the cingulated gyrus and amygdala before continuing to the nucleus accumbens and the ventral part of the globus pallidus, and returns via the mediodorsal nucleus of the thalamus to the supplementary motor area and premotor cortex.
Changes in dopaminergic transmission
The indirect pathway serves to stimulate GPi-SNr, while the direct pathway inhibits GPi-SNr. Dopaminergic neurons exert a stimulatory effect on the direct pathway via D1 receptors and exert an inhibitory effect on the indirect pathway via D2 receptors, the overall effect being an inhibition of the GPi-SNr
When more than 70% of dopaminergic neurons undergo cell death, symptoms of Parkinsons’s occur. This is because with the death of dopaminergic neurons, the brake on glutaminergic stimulatory transmission in the indirect pathway is lifted, and the direct pathway is inhibited. Overall, GPi-SNr is overly stimulated, causing an overinhibition of cells in the ventral tier of the thalamus, reducing greatly the stimulation of the striatal cells by the thalamus. Negative feedback occurs in the striatum and its activity is greatly reduced. This accounts for the bradykinesia or akinesia occurring in patients. Other symptoms are tremor, rigidity and postural instability.
There are 3 hypotheses for the death of dopaminergic neurons. First, it is believed that mitochondrial damage plays a part. Rotenone or MPTP may damage mitochondrial complex I, disrupting the flow of electrons, thus resulting in free radical formation. Lipid peroxidation occurs, and 4 hydroxynonenal is formed as a by product. 4 hydroxynonenal disrupts the function of proteins in the cell membrane.
Secondly, alpha synuclein may aggregate. It is intrinsically unstructured hence it has great conformational plasticity. It can form monomers and oligomers, resulting in the formation of amyloidogenic aggregates. These aggregates damage the cell in the following ways: by causing a toxic gain of function reaction, by forming large intracytoplasmic inclusions, by increasing synthesis of wild type alpha synuclein
Thirdly, the Parkin protein plays a part. It is linked to 6q25q27 which is linked to early onset of Parkinson’s. Parkin is a ubiquitin ligase and because it reduces the levels of ubiquitin, extra intracellular proteins cannot be tagged by ubiquitin for destruction. Cellular junk accumulates, damaging the cell.
Drugs for Parkinson’s disease.
L-dopa is an immediate metabolic precursor of dopamine. It can cross the blood brain barrier via uptake by receptors, and thereafter it is decarboxylated into dopamine, thus serving to depress the indirect pathway. It is used in very elderly patients (above 80 yrs old) or in patients with a life-threatening or career-threatening form of the disease
COMT inhibitors reduce the formation of a competitive antagonist of dopamine, 3 methyl dopamine, through inhibiting the enzyme. As a result, the effects of dopamine are enhanced.
Dopamine agonists are given to treat bradykinesia. The old generation drugs include bromocriptil and pergolide. Having long half lives, they prolong the effects of L-dopa. The newer generation drugs are pramiterol and ropinirole, which are more selective. Amantadine is also a dopamine agonist given to elderly patients.
Seleginine is a MAO inhibitor and inhibits the breakdown of dopamine. It is given in patients without clinically significant disabilities. Consider also sending these patients to research centres for trials to be conducted on them
Ach inhibitors can also be given to treat tremor. They are given to elderly patients
Surgery can also be used. An example of non lesional surgery is deep brain stimulation. DBS of the globus pallidus treats tremor and dyskinesia, DBS of the subthalamic nucleus treats akinesia. DBS of the thalamus is best for treating tremors which are worse on one side of the body than the other
Lesional surgery can also be performed. Examples are VM thaladotomy, used to treat tremors, and medial pallidotomy, used to treat dyskinesias.
There may be errors here and there. And not to mention I took almost one hour to type this, so tml I have to omit some details