BISC 421 1st Edition Lecture 14 Outline of Current LectureI. Synaptc Plastcity II Current LectureI. Basal Ganglia •Describing a restng tremor- parkinsons disease•This is an inherited disease•Biological foundaton for these diseases•Basal ganglia: caudate nucleus and putamen form the striatum•Substanta nigra divided into two parts. In brainstem•Globus palludus (*palladum)- divided into two parts•The key players are listed on the right compose the basal ganglia--Dopaminergic neurons excite some medium spiny cells and inhibit others, as we will see.Medium spiny neurons receive many excitatory cortcal inputs, though each inputcontributes little.•Circuits and connectvity among these structures: medium spiny neurons have 3 different projecton targets: know these three•On right is a wiring diagram from book: medium spiny neurons receive many excitatory cortcal inputs and each input contributes just a little depolarizaton•They are silent unless they are excited (gabaergic)•Cells in the globus palladus are always actve unless inhibitedCortcal inputs to the striatum are not only topograhically mapped with respect to the body, but functonally divided as well.The caudate receives info from multmodal (e.g. multsensory) associaton cortces and frontal eye fields. The putamen receives info from somatosensory, visual, premotor and motor cortcesThe putamen tends to discharge in antcipaton of body movements- Just remember that there is a topographic representaton of the body in the putamen•Topography of the striatum•There is a lot of overlap•General topography in the basal ganglia•Basal ganglia involved in the producton of motonThere are non motor loops and motor loops (regulate upper motor neurons for coordinaton of voluntary movement)•Two main motor pathways: work together but think of them as different pathways•The putamen is sending a lot of inhibiton to the glob pal in which will become more actve and will send a large signal to the thalamus (remove some of the inhibiton)•Get to a net excitaton by a lot of disinhibiton•Cotex sends large signal to putamenmedium spiny neurons send signal to glob pal ext that is inhibitory if we inhibit actvity here we get lesser inhibiton coming into the sub thalamic nucleus projects to glob pal int which is a large signalincreased actvity in the glob pal int sends a large amount of inhibiton to the motor thalamus reduces the amount of excitaton the cortex receives•Turning on the “brakes”•MEMORIZE THESE PATHWAYS•Role of dopamine•Excites the direct pathway via D1 receptors and inhibits the indirect pathway via D2receptors•Net excitatoryMedium spiny cells that project to the Glob. Pal. Int. are excited by dopamine via D-1 receptors•Black because of the dopamine synthesizing neurons•In case of the direct pathway dopamine is positve- some spiny neurons that are excited by dopamine via D1 receptor•Indirect pathway responds to dopamine with inhibiton via D2 receptors- different spiny neurons that have these receptors•Project to the Globulus pal ext•Kinesia- movement•Hemiballismas- effects one side of the body•Huntngtons disease- due to mutaton in a gene•These both lead to unregulated movement•Parkinsons- inability to initate movement•Drug induced problems- neuroleptc drugs lead to parkinsonian effects•Healthy brain on right and unhealthy brain on lef•Healthy black stripe on right•Pill rolling tremor- tremor at rest•Know these pathways backwards and forwards•When we lose dopamine: for direct pathway there is less excitaton•For indirect pathway- more inhibitonCortexGlutamate (+)PutamenGABA (-)Glob. Pal. ext.Glutamate (+) GABA (-)*Sub Thal. Nuc.Glutamate (+)*Glob. Pal. Int.GABA (-)*VA/VL ThalamusWhen the subthalamic nucleus is lost, actvity in Glob. Pal. Int. is reduced– the VA/VL receives too little inhibiton and goes into overdrive and over excites cortex.•If we lose dopamine we lose the ability to initate movement•Loss of the subthalmic nucleus•Glob pal int goes into overdrive •Loss of striated neurons and overall loss of cortcal tssue•Leads to change in coordinaton and involuntary movementsLoss of the Putamen reduces inhibiton of the Glob. Pal. ext , which results in increased cortcal actvity•Putamen is the same as striatum which is what we lose in this disease•Increase cortcal actvity•There is no cure•Can be alleviated by a form of dopamine•Recent studies•Not on
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