Plum and posner’s diagnosis of stupor and coma fourth Edition series editor sid Gilman, md, frcp
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Box 1–2 The Thalamus, Basal Forebrain, and Generation of EEG Waves The origin of the sinusoidal appearance of the waveforms in the EEG remained a mystery until the 1980s. Although it was understood that the EEG voltages are due to the summated excitatory postsynaptic potentials in dendrites of cortical neurons, the reason for the synchronous waves of dendritic potentials remained elusive. The waves of postsynaptic potentials in the cerebral cortex are now un- derstood to be due to the intrinsic burst firing of neurons in the thalamus, basal forebrain, and the cortex itself, which produce waves of postsynaptic potentials in cortical neurons. When the membrane potential of burst neurons is close to their firing threshold, they fire single action potentials that transmit sensory and other information. How- ever, when burst neurons have been hyperpolarized to membrane potentials far below their usual threshold for firing sodium action potentials, a low-threshold calcium channel is deinactivated. When the low-threshold calcium channel is trig- gered, calcium entry brings the membrane potential to a plateau that is above the threshold for firing sodium action potentials. As a result, a series of sodium spikes are fired, until sufficient calcium has entered the cell to activate a calcium-activated potassium current. This potassium current then brings the cell back to a hyperpo- larized state, terminating the burst of action potentials. The more deeply the resting A B
Slow-wave sleep Bursts
Bursts Ca 2+ Na + 100 ms 50 mV Single spikes Single spikes Thalamic
firing intracellular Thalamic firing
extracellular EEG
0.5 s Figure B1–2. Thalamic relay neurons have transmission and burst modes of firing. (A) During transmission mode, which operates mainly during wakefulness, individual neurons in the thalamus fire single spikes in patterns that reflect their incoming afferent inputs. This correlates with a desynchro- nized electroencephalogram. (B) During burst mode, the thalamic neurons are hyperpolarized by gamma-aminobutyric acid (GABA)-ergic afferents, deinactivating a low-threshold calcium current with a long plateau. This brings the cell above the threshold for firing sodium action potentials, which are fired in a burst, until this is terminated by a calcium-activated potassium current that hyperpolarizes and silences the cell. These bursts tend to fire rhythmically, in correspondence with high-voltage slow waves in the EEG, which reflect large volleys of synchronized excitatory inputs reaching cortical dendrites. (From Saper, C. Brain stem modulation of sensation, movement, and consciousness. Chapter 45 in: Kandel, ER, Schwartz, JH, Jessel, TM. Principles of Neural Science. 4th ed. McGraw-Hill, New York, 2000, pp. 871–909. By permission of McGraw-Hill.) (continued) 13
a wakeful state. 32 Thus, the lower brainstem was thought to play a synchronizing, or sleep- promoting, role. 33 Transections from the ros- tral pons forward produced EEG slowing and behavioral unresponsiveness. Periods of fore- brain arousal returned after several days if the animals were kept alive. However, it is clear that the slab of tissue from the rostral pons through the caudal midbrain (the mesopon- tine tegmentum) contains neural structures that are critically important to forebrain arousal, at least in the acute setting. At the time, little was known about the ori- gins of ascending projections from the meso- pontine tegmentum to the forebrain, and the arousal effect was attributed to neurons in the reticular formation. However, more recent stud- ies have shown that projections from the meso- pontine tegmentum to the forebrain arise from several well-defined populations of neurons. The major source of mesopontine afferents that span the entire thalamus is a collection of cho- linergic neurons that form two large clusters, the pedunculopontine and laterodorsal tegmen- tal nuclei. 34 These neurons project through the paramedian midbrain reticular formation to the relay nuclei of the thalamus (which innervate specific cortical regions), as well as the midline and intralaminar nuclei (which innervate the entire cortex more diffusely), and the reticu- lar nucleus. As noted in Box 1–2, the reticular nucleus plays a critical role in regulating thala- mocortical transmission by profoundly hyper- polarizing thalamic relay neurons via GABA B receptors. 35 Cholinergic inputs in turn hyper- polarize the reticular nucleus. Other neurons in the cholinergic pedunculopontine and later- odorsal tegmental nuclei send axons into the lateral hypothalamus, where they may contact populations of neurons with diffuse cortical pro- jections (see below). Neurons in the pedun- culopontine and laterodorsal tegmental nuclei fire fastest during REM sleep (see Box 1–3) and wakefulness, 36 two conditions that are charac- terized by a low-voltage, fast (desynchronized) EEG. They slow down during non-REM (NREM) sleep, when the EEG is dominated by high-voltage slow waves (Figure B1–3A). membrane potential of the cells is hyperpolarized, the less frequent but longer the bursts become. The bursting behavior of neurons in the thalamic relay nuclei, which are a major source of cortical inputs, is often thought to be a major source of cortical EEG. The synchrony is credited to the thalamic reticular nucleus, which is a thin sheet of GABAergic neurons that covers the thalamus like a shroud. Thalamic axons on their way to the cerebral cortex, and cortical projections to the thalamus, give off collaterals to the reticular nucleus as they pass through it. Neurons in the re- ticular nucleus provide GABAergic inputs to the thalamic relay nuclei, which hy- perpolarizes them and sets them into bursting mode. However, there is evidence that the synchrony of EEG rhythms across the ce- rebral cortex is due in large part to corticocortical connections, and that even isolated slabs of cortex can set up rhythmic slow-wave potentials. 26 Recent evidence suggests that the basal forebrain may play a critical role in entraining cortical rhyth- mic activity. Basal forebrain neurons also fire in bursts that are time-locked to cortical rhythms. In addition, cell-specific lesions of the basal forebrain can elimi- nate fast cortical rhythms, including those associated with wakefulness and rapid eye movement (REM) sleep, whereas large cell-specific thalamic lesions have sur- prisingly little effect on the cortical EEG. 27 Thus, the waveforms of the cortical EEG appear to be due to complex interac- tions among the burst neurons in the thalamus, cortex, and basal forebrain, all of which receive substantial inputs from the ascending arousal system. Box 1–2 The Thalamus, Basal Forebrain, and Generation of EEG Waves (cont.) 14 Plum and Posner’s Diagnosis of Stupor and Coma Yüklə 6,14 Mb. Dostları ilə paylaş:
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