For those who (pretend to) care...

For those two people genuinely interested and others faking interest ; the following section is the general abstract that preceeds the research chapters in the report of my nine month internship. It is as short as I can write it down without leaving out the real important information. I wonder if anyone will actually read it, but....

"The cerebellum is the part of the brain that is crucial in the coordination of reflexive movement. For the maintenance of balance by postural adjustment the cerebellum receives information from the vestibular system, the visual system and proprioceptors in muscles and joints. The cerebellum output signal is used for the necessary compensating movements. This output signal is provided by one singe cell type; the Purkinje cell. This means that understanding how the Purkinje cell’s discharge pattern is modulated is an important step towards understanding the cerebellum and its computational circuitry. Purkinje cells have two distinct types of action potential; climbing fiber responses (CFRs) and simple spikes (SSs). CFRs are multi-peaked action potentials with a low frequency and long duration. SSs are single peak action potentials, with a much higher discharge frequency and shorter duration. There are two major input pathways from the vestibular apparatus to the Purkinje cell. Primary vestibular afferents project as mossy fibers on granule cells in the ipsilateral uvula-nodulus of the cerebellar cortex. Granule cell axons form parallel fibers that synapse on Purkinje cell dendrites. One Purkinje cell receives synapses from up to ~150,000 parallel fibers. Primary vestibular afferents also project to the ipsilateral inferior olive through the parasolitary nucleus. From the inferior olive climbing fibers ascend to the contralateral cerebellar cortex where they synapse on only a few Purkinje cell dendrites. Each Purkinje cell only receives input from one climbing fiber. Purkinje cell discharge patterns can be modulated by vestibular stimulation. Sinusoidal oscillations about the longitudinal axis causes CFR frequencies to increase and SS frequencies to decrease in Purkinje cells ipsilateral to the side that is down during stimulation. In contralateral Purkinje cells this modulation in reversed; CFRs decrease and SSs increase. This antiphasic modulation of CFRs and SSs raises the question if those two types of action potentials are modulated independently or correlated. CFRs are evoked by the climbing fibers and their modulation directly reflects climbing fiber activity. SS modulation is less well understood. A first thought might be to attribute SS modulation to the numerous parallel fiber synapses on the Purkinje cell. But vestibular primary afferents are modulated out of phase with SS discharge and there is no inhibitory synapse in the mossy mossy fiber-granule cell-parallel fiber pathway to the Purkinje cell. Furthermore, experiments in the rabbit and mouse show that after elimination of primary vestibular afferents by a unilateral labyrinthectomy, modulation of CFRs and SSs persists. This means the modulation can not be attributed to the mossy fiber-granule cell-parallel fiber input to the Purkinje cell. Lesions in the inferior olive greatly reduce CFR and SS modulation in the contralateral uvula-nodulus suggesting that climbing fiber activity is the driving force behind both CFR and SS modulation. Modulation of climbing fiber activity is also out of phase with SS modulation, which makes a direct modulation unlikely. Besides Purkinje cells there are also interneurons in the cerebellar cortex that might play a role in SS modulation. Stellate cells are the only interneurons that have the suitable characteristics to inhibit SS discharge. They are modulated in phase with climbing fiber activity and have inhibitory synapses on the Purkinje cell. During increased climbing fiber activity the increased stellate cell inhibition could account for the decrease in SS discharge. How the stellate cells are modulated by climbing fiber activity is unknown since there are no climbing fiber synapses on the stellate cell. Glial astrocytes might have something to do with this. The location of Bergmann glial cells at the climbing fiber-Purkinje cell synapse allows them to sense climbing fiber activity by neurotransmitter transients. They secrete glutamate and diazepam binding inhibitor that could increase the excitability of stellate cells. Attempts to model this hypothesized circuitry in a realistic model of the cerebellar cortex have been abandoned for the time being. Ideas to use a realistic compartmental model of Purkinje cell in the GENESIS modeling software have stranded due to an initial misinterpretation of the Purkinje cell model and a lack of time and resources. Purkinje cell discharge in the uvula-nodulus is modulated by stimulation of the vestibular apparatus. The functional role of the nodulus for the execution of compensatory movements can be investigated with a newly proposed behavioral experiment that measures the displacement of the center of mass and compensatory head movements in the mouse, during vestibular and optokinetic stimulation. Also, new cell-specific RNA interference techniques will be developed to knock down the function of specific interneurons in vivo. With this technique the possible necessity for SS modulation of stellate cells and other interneurons can be tested. This might ultimately lead to an explanation of the modulating circuitry behind the cerebellar output signal."

So you skipped it right? Or did you actually read it? In that case; hats off to you! You have earned the reward. You are invited to a party at my house in Utrecht november 25thor 26th. One of my housemates just returned from a long stay in australia and I will be back next week. Enough reason for a party. Or so I was told today when I heard about the party. Must agree though, it will be a great opportunity to catch up with people I haven't seen for the past six months...