1. Summary of Lecture 3 VETS2011 Cerebellum Demo of VOR in owl: VOR plasticity World record cerebellum: Electric fish: nanosecond timing Summary of structure and function in cerebellum Time-to-place conversion Adaptive plasticity of VOR (Owl, “wet head example”) Contrast procedural learning with declarative memory

3. Procedural Memory Gain of reflexes (e.g. VOR) Conditioned reflexes (e.g. eye blink) Skilled sequences (e.g. cycling, typing)

4. Vestibulo-Ocular Reflex (VOR) Fastest reflex in brain Operates “perfectly” without cerebellum (i.e. same conditions) But gain adaptation requires cerebellum (i.e. as conditions change, such as growth, ageing, muscle strength, oxidative damage etc)

5. VOR circuit: 1. Vestibular hair cell 2. Vestibular neuron 3. Oculomotor neuron Only 2 synapses. Purkinje cell modulates VOR reflex at vestibular neuron

6. Trout Electric Fish

7. Basic fishElectric Fish

9. Forebrain Cerebellum

10. Purkinje Cell. Only output of cerebellum GABAergic inhibition 10 6 spine synapses Spines modifiable by LTD Climbing fibre“Punishes” co-active spine synapses “Espalier “ shape enables tight packing in coronal plane despite huge sagittal arbour: gives “delay line”.

11. Excitatory Inputs. Mossy fibre to granule cells to parallel fibres to spine synapses on Purkinje cells Vast combinations provide the sensory context Sensory context

12. Climbing fibre Covers whole dendritic tree of Purkinke cell All-or-nothing acitvation Co-activation of climbing fibre and parallel fibre Leads to LTD of the parallel fibre synapse.

13. Interneurons. Golgi for Granule cells Basket and Stellate for Purkinje cells Inhibitory (GABA, glycine etc) Diversity increases With cerebellar complexity (greatest variety in anthropoid primates)

14. 1 2 3 4 Time-to-Place Conversion: Purkinje cells along “beam” of parallel fibres e.g. 10 m/sec gives 10 mm/msec or 10  m/  sec. So a 10  m spacing between Purkinje cells allows a time resolution of 10  sec. Electric fish achieve nanosecond timing with larger, faster beams.

15. Time-to-Place Conversion: Purkinje cells along “beam” of parallel fibres e.g. 10 m/sec gives 10 mm/msec or 10  m/  sec. So a 10  m spacing between Purkinje cells allows a time resolution of 10  sec (humans). Electric fish achieve nanosecond timing with larger, faster beams. 10 20 30 0  sec

16. Declarative vs Procedural Memory Forebrain: Bilateral Single trial possible “Creative”; fraction of inputs LTP cAMP 2nd messager Error-prone ?Sleep needed Hindbrain:Midline Many trials needed “Stupid”: needs all inputs LTD cGMP 2nd messager Precise Corrected in waking state