2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework** Consortium leader PETER PAZMANY CATHOLIC UNIVERSITY Consortium members SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BEVEZETÉS A FUNKCIONÁLIS NEUROBIOLÓGIÁBA INTRODUCTION TO FUNCTIONAL NEUROBIOLOGY www.itk.ppke.hu By Imre Kalló Contributed by: Tamás Freund, Zsolt Liposits, Zoltán Nusser, László Acsády, Szabolcs Káli, József Haller, Zsófia Maglóczky, Nórbert Hájos, Emilia Madarász, György Karmos, Miklós Palkovits, Anita Kamondi, Lóránd Erőss, Róbert Gábriel, Zoltán Kisvárday, Zoltán Vidnyánszky Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu ThalamusImre Kalló & László AcsádyPázmány Péter Catholic University, Faculty of Information Technology I. Thalamic nuclei relaying peripheral signals to the cerebral cortex. Input from the cortex and the reticular nucleus of the thalamus. II. Thalamo-cortical rhythms. Tonic and burst activity pattern of relay cells. III. Thalamic nuclei, activity of which reflect higher cognitive processes. IV. The extrareticular inhibition. Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu Corticocentral world concept D. van Essen Ctx1 Ctx2 Ctx3 Thalamus Periphery Faithful transfer of the peripheral information (relay function) Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu Ctx1 Ctx2 Ctx3 Thal Periphery Ctx1 Ctx2 Ctx3 Thal 1 Periphery Thal 2 ? Thalamic input is required to all (studied so far) cortical functions Corticocentral world concept Thalamocortical world concept The higher order neuronal function is based on cortico-cortical connections Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu Ctx1 Ctx2 Ctx3 Thal Periphery Ctx1 Ctx2 Ctx3 Thal 1 Periphery Thal 2 ? Thalamic input is required to all (studied so far) cortical functions Corticocentral world concept Thalamocortical world concept The higher order neuronal function is based on cortico-cortical connections The unknown thalamus Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu The case of Karel Ann Quinlan • There was a transitional circulatory-respiratory arrest at her age 21 year. • After resuscitation her autonomic functions returned, but never gained her consciousness back. She remained in persistent autonomic state. • She died ten years later. What was lesioned in the nervous system of Karen Ann Quinlan ? KAQ1 KAQ3 Kinney et al., 1994 KAQ2 KAQ4 Kinney et al., 1994 Negligible lesion in the cerebral cortex Serious defect in the thalamus Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu Basic concepts of thalamic organisation Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu The „driver” concept Actvity response of a VPM relay cell to whisker stimulation VPM_evoked1 Lavallée et al. 2005 JNsci Driving input Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu Topographic organization and specificity of modalities The relay function B89VB Different types of somatosensory responses recorded in the monkey thalamus Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu Topographic organization and specificity of modalities The relay function Tonotopic representation in the cat thalamus 622MGN Imigand Morel 1985 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu The source of „modulators” vGLUT1 –cerebral input Modulator –small axon terminal Target -distal dendrite One bouton one synapse Cerebral cortex VI. layer Subcortical centre Thalamus Cerebral cortex Periphery vGLUT2 –subcortical input Driver –large axon terminal Target -proximal dendrite One bouton many synapse Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 www.itk.ppke.hu All thalamic regions receive an order of magnitude more input from the VI. layer of the cortical area, which they innervate, than from the periphery. The cortical feed-back 226VB Thalamus Periphery Cerebral cortex VI. layer Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 www.itk.ppke.hu The VI. layer afferent: • Small • It establishes a single synapse • On the distal dendrite The cortical feed-back Thalamus Periphery Cerebral cortex VI. layer EM2 The „modulator” cortical afferent Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 www.itk.ppke.hu VPM -Inactivation of the cerebral cortex hardly influences the transfer of the peripheral stimulus The cortical feed-back thal2 Thalamus Periphery Cerebral cortex VI. layer Diamond et al., 1992 Whisker stimulation-evoked response in the rat somatosensory thalamus, when the cerebral cortex was inactivated. Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 www.itk.ppke.hu Nucleus reticularis thalami -nRT TC Ctx. VI. layer nRT 01Keszkepkis_x2,5 nRT nRT nRT KCC2 PV PV-KCC2 VPL VPM Po Desilets-Roy2002JNsci The thalamic inhibition: ThenRT ensures a precise topographic inhibition in all thalamic nuclei. Both thecorticothalamic cells in the VI. layer, and the thalamocortical cells provide axon collaterals to the nRT. Desilets-Roy et al., 2002 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 www.itk.ppke.hu Three members of the thalamocortical circuit B51rele TC –thalamo-cortical relay cell excitatory Cx -VI. layer cortical corticothalamic pyramidal cell excitatory RE -n. reticularis cellinhibitory Cx RE TC Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 www.itk.ppke.hu Thalamocortical rhythms 775sumslow Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 www.itk.ppke.hu Brain-computer interface: movement of cursor with the aid of . (µ) waves Wolpaw and McFarland 2004 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 www.itk.ppke.hu Slow wave sleep, sleep spindles and learning Declarative memory task -controls received a task unrelated to learing The density of sleep spindles was in correlation with the success of recall before and after sleep Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 21 www.itk.ppke.hu Huber et al. 2004 Learning –Specific increase of delta wave performance in the affected cortical field Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 www.itk.ppke.hu Jeanmonod1 Thalamocortical dysrhythmia Common pathophysiologic alterations can be found in the background of different neurological and neuropsychiatric symptoms. 3-4Hz rhythmic relay cell activity and slow EEG oscillation in awake state . Jeanmonod 1996 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 www.itk.ppke.hu EEG activity in the different phases of the sleep-wake cycle sleep_eegs Awake:high frequency small amplitude activity Non-REM sleep:low frequency high amplitude activity REM sleep:the same as in awake state Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 24 www.itk.ppke.hu Fast rhythmic EEG activity in the cat parietal cortex during focused attention AW921 Rougel-Buserand Buser1994 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 25 www.itk.ppke.hu Mechanisms of formation of thalamocortical rhythms B51rele LTS5 INa IA IT During different rhythms, activity is determined by the internal characteristics AND synaptic connections of the cells. The system shows stable (resonant) characteristics in several different states. Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 www.itk.ppke.hu Two different types of firing mode of the relay cells Burst vs single spike 51current A) Different types of action potentials triggered by different current injections at various membrane potentials B) The same phenomena induced by stimulating the excitatory afferents C) burst activity following IPSPs Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 www.itk.ppke.hu Reliability of signal transfer in tonic and burst mode of the firing activity of thalamocortical cells 55current Awake-„tonic mode”the activity of relay cells precisely mediates the afferent signal towards the cerebral cortex Sleeping-„burst mode”the activity of relay cells does not follow the frequency of the afferent signal During sleep,by means of the burst activity, the thalamus cuts off the cerebral cortex from the external world. McCormick and Feeser, 1990 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 www.itk.ppke.hu The two types of firing pattern of the thalamocortical cells The T-type calcium channel LTS5 INa IA IT LTS4 INa IA Tonic firing Burstfiring Tonic:depolarised membrane potential, single Na+/K+ action potentials (INa, IA) Burst:hyperpolarised membrane potential, Ca2+mediated depolarization „riding” Na+/K+ action potential train IT –low threshold calcium-channel two activation gates -it is inactive at resting potential –it can not open –there is no Ca2+-influx -it becomes de-inactivated in response to hyperpolarization (it turns into an activable state –there is no Ca2+-influx) -in response to a subsequent depolarization it becomes activated -huge Ca2+influx –it causes depolarization, which may induce a Na/K action potential train (burst) Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 www.itk.ppke.hu The two types of firing pattern of the thalamocortical cells The H current 58IH Mixed kationic current opened by membrane hyperpolarization . It acts against hyperpolarization by depolarising the cell. „Pacemaker current” Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 www.itk.ppke.hu The interaction of the two currents at hyperpolarised membrane potential leads to oscillation, rhythmic burst activity 511summary McCormick and Pape, 1990 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 31 www.itk.ppke.hu In relay cells, the burst firing pattern is changed to tonic in response to acethylcholine and norepinephrine 818subco Be1511 REM415 The brainstem ascending activating system Function of the brainstem „waking” cells during the sleep-wake cycle Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 32 www.itk.ppke.hu Origin of the 7-14 Hz spindle activity in the thalamus 712spindle nRt – slowdepolarizationwave, burstswithspindle frequency Relaycells – rhythmic IPSP sequences, sometimeslowthreshold burst activity Cortical pyramidal cell – rhythmic EPSP, sometimes action potentials Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 33 www.itk.ppke.hu Synchronous oscillation of cortical and thalamic neurons during spindle 735spindle Spontaneous spindle activity Correlated activity between: -the EEG -the cortical intracellular -and the nRt extracellular events. Contreras and Steriade, 1995 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 34 www.itk.ppke.hu TC Ctx. layer VI nRT 775sumslow The thalamocortical circuit The three, continuosly interacting cell types generate the thalamocortical oscillations extending to the whole brain. Steriade et al., 1997 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 35 www.itk.ppke.hu The cortical response is enhanced following stimulation of the thalamus or after spontaneous spindle activity Steriade_aug_spindle Intracellular recording from cortical fast spiking cells Before stimulation/spindle : In response to the cortical stimulation, the cellular response is an action potential After stimulation/spindle: In response to the cortical stimulation, the cellular response is an action potentialtrain Steriade 2004 Introduction to functional neurobiology: Thalamus 2011.10.15.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 36 www.itk.ppke.hu SUMMARY Accordingly to the sleep-wake cycle, the relay cells show tonic and burst activities. Rhythmic burst activity may evolve merely due to the internal membrane characteristics of the relaycell. Thalamocortical oscillationis realized by the interaction of therelay, the nRtand thecorticothalamiccells. The largeamplitude rhythmic oscillationsduring sleep may play a role in long-term fixation of certain memory traces.