Cellular neurophysiology

Transcription

1 Cellular neurophysiology Katalin Schlett Dept. Physiology and Neurobiology tel: 8380 ext; room recommended literature: From Molecules to Networks: An Introduction to Cellular and Molecular Neuroscience Eds: John H. Byrne, James L. Roberts. Academic Press, 2nd Ed., ISBN: Fundamental Neuroscience. Eds: L.R. Squire, D. Berg, F.E. Bloom, S. du Lac, A. Ghosh, N.C. Spitzer. Academic Press, 4th Ed., ISBN: scientific papers!

2 Major cellular components of the nervous system - overview

3 Cellular components of the brain brain tissue: skull pia mater oligodendroglia microglia Ranvier node astroglia myelin sheat neuron axon neuron astroglia capillary dendrite ependyma ventricule microvillus human brain : ~10 11 neuron x glia cell (or 1:1 ratio? J. Comp. Neurol. 513(5): )

4 basic structure of neurons axon side branch (collateral) dendrites axonal hillock axon soma myelin sheat oligodendroglia / Schwann cells Ranvier-node Nissl-body (ribosome) nucleus axonal citoplasm axon terminal presynaptic terminal spread of (de)polarisation

5 basic functions of neurons dendrite synapses terminally differenciated, highly specialized cells soma nucleus axon hillock AP initiation integration of electrical inputs pre-synapse synapse axon myelin sheath spread of AP synaptic cleft postsynapse vesicule axon terminal transmitter release

6 morphology dendritic spines (S) narrow spine necks (asterisks) dendritic shaft (D) spine apparatus particularly visible in the lower panel spine postsynaptic densities of asymmetric excitatory synapses (arrows) apposed axonal boutons (B) two symmetric inhibitory synapses (arrowheads) on a large dendritic shaft (D) axonal boutons (B) contain some ovoid vesicles compared to the ones in asymmetric synapses dendrites and axons contain numerous mitochondria (m) General neuronal features - axon / dendrite - dendritic tree, dendritic spines - synapse symmetric (Gray II): variable, large vesicles; inhibitory asymmetric (Gray I): small, round vesicles; mainly excitatory

7 General neuronal features high number, enormous diversity, huge amount of synaptic connections - human brain: ~10 11 neuron neocortex: ~2x10 10 neuron, ~ 1.5x10 14 cortical synapses; length of myelinated fibers ~ km - macro- and micronetworks - main types: local inhibitory interneurons (eg. GABAerg interneurons) local excitatory interneurons (eg. spiny stellate cells) inhibitory projection neurons (eg. Purkinje cells) excitatory projection neurons (eg. pyramidal cells, motoneuron) neuromodulatory cells (pl. substantia nigra dopaminergic cells)

8 General neuronal features - main neuron types within the cortex: excitatory - locally projecting layer 4 neurons - cortico-cortical projection neurons - subcerebral projection neurons (pyramidal tract neurons), - cortico-thalamic projection neurons - layer 6b subplate neurons inhibitory - parvalbumin-expressing (PVALB+) cells, - somatostatin-expressing (SST+) cells, - vasoactive intestinal peptide-expressing (VIP+) cells - cells expressing 5-hydroxytryptamine receptor 3A but lacking VIP (HTR3A+/VIP-) - additional classification based upon morphology, transmitter or Ca-binding protein content, firing patterns, etc (see eg. )

9 General neuronal features anatomical classifications: based on morphology and outline of innervations

10 molecular classification (PV, SST, NPY/SST -, VIP, CCK/SST -, VIP - ) General neuronal features

11 molecular classification: based on transcriptome analyses (single-cell RNA sequencing) General neuronal features

12 General neuronal features classification upon the characteristics of neurites / branches

13 General neuronal features

14 General neuronal features characterisation upon firing patterns

15 General neuronal features

16 General neuronal features postmitotic cells, no further cell divisions extreme surface-to-volume ratio - eg. a sensory neuron ~ 10-6 g weight;general soma-size is approx mm, nuclear diameter 3-18 mm; average membrane surface is ~ mm 2 The 1-μm axon of a cortical neuron, projecting 100 cm into the corticospinal tract, can be compared to a 4-m-wide subway tube that is 4,000 km long. To extend the metaphor, fast axonal transport (of mitochondria, at 5 μm/s) is analogous to a train travelling at 70 km/h, whereas slow axonal transport (of proteins, at 2 mm/day) is, by analogy, slower than a pedestrian (0.5 km/h). Neurons with long axons, therefore, present a logistical problem, and are a vulnerable bottleneck for the entire nervous system. specialized, mosaic membrane segments and regions - somatodendritic <-> axonal regions - pre- and postsynaptic structure, dendritic spines - myelinated <-> naked surfaces - adhesive <-> secretory membrane regions

17 General neuronal features most polarized cells - apical ~ axonal region - basolateral ~ somatodendritic region - directed organelle, protein and membrane (vesicular) transport - polarised cytoskeleton specialised migratory activity - site of last mitosis and the final position of the soma is normally separated: soma translocation happens mainly without neurite outgrowth (cortical pyramidal neurons: inside out migration; cerebellar granule neurons: outside-in migration; cortical interneurons: tangential migration) -neurite outgrowth starts normally only after the soma reaches its final position -> neuronal plasticity

18 General neuronal features specialised intracellular transport - extreme and intensive membrane turnover - high energy consumption, across long distances - polarised cytoskeleton and transport / motor proteins - anterograde <-> retrograde directions local <-> distal (soma) protein synthesis special secretory activity - neurocrine secretion: normally one type of neurotransmitter, via synapses - general secretory activity: neuromodulators, growth factors fast spread of potentials - electrical conductance synaptic communication

19 General oligodendroglia features CNS myelin sheath (PNS: Schwann cells) - from vertebrate origins x increase in the speed of conductance mm internodal segments

20 General astroglia features 20-50% volume of total brain parenchyme - radial / plasmal / fibrillyary GFAP content! - pia mater ependyma: glia limitans diverse functions: covering neuronal and oligodendroglia surfaces, insulation secretion of ECM components and growth factors spatial buffering metabolic regulation and effects: Gln Glu cycle reactive gliosis regulation of the neurovascular unit

21 General astroglia features

22 General microglia features CNS tissue macrophages - no ectodermal origin! : mesoderm / bone marrow origin 5-20% of the normal brain tissue normal and reactive features: - changes in morphology - secretion of cytokines and other growth factors

23 Essay questions Explain the main characteristics of neurons, highlighting their specific features, as well! / Ismertesse az idegsejtek általános jellemzőit! Emelje ki az idegsejtek speciális tulajdonságait is! Explain the drawbacks and difficulties of neuronal classification, hindering the description of proper and reproducible neuronal subtypes! What kind of limitations are faced by the researchers? / Milyen korlátokkal néznek szembe az idegsejtek klasszifikációjára, azaz típus szerinti csoportosítására és osztályozására irányuló törekvések?

24 Recommended literature Nat Rev Neurosci Sep;18(9): doi: /nrn