Sleep-Wake Cycle I Brain Rhythms Reading: BCP Chapter 19
Brain Rhythms and Sleep Earth has a rhythmic environment. For example, day and night cycle back and forth, tides ebb and flow and temperature varies with the seasons. To compete effectively and survive, an animal s behavior must oscillate with the cadence of its environment. Brains have evolved a variety of systems for rhythmic control; some fast (e.g., electrical) some slow (e.g., circadian). The sleep-wake cycle is a striking example of periodic behavior that reflects the activity of a number of brain rhythms.
The Electroencephalogram The electroencephalogram (EEG) is a measurement of electrical activity from the surface of the scalp that enables a glimpse of the generalized activity of the cerebral cortex. Wires from pairs of electrodes are fed to amplifiers, and each recording measures voltage differences between two points on the scalp. The EEG is used primarily for research purposes (notably the study of cognitive processes during wakefulness and of the stages of sleep) and to help diagnose certain neurological diseases (e.g., epilepsy).
Generation of Electrical Fields 1 An EEG measures voltages generated by the currents that flow during synaptic excitation of the dendrites of many pyramidal neurons in the cerebral cortex, which lies right under the skull. The electrical contribution of any single cortical neuron is small, and the signal must penetrate many layers of tissue to reach the electrodes. Therefore, it takes many thousands of underlying neurons, activated together, to generate an EEG signal big enough to be measured.
Generation of Electrical Fields 2 The amplitude of the EEG signal strongly depends on how synchronous is the activity of underlying neurons. asynchronous: EEG signal is small synchronous: EEG signal is large It is not necessarily the number of activated cells, or the total amount of excitation, that creates a large EEG signal but the timing of activity is critical. Asynchronous
Magnetoencephalography (MEG) An alternative way to record the rhythms of the cerebral cortex is via MEG. Whenever current flows, magnetic fields are generated. MEG scanners (which are large and expensive) can detect the tiny magnetic signals produced by synchronously active neurons. Magnetic fields are less distorted than electrical fields by tissue, so MEG is much better at localizing the sources of neural activity in the brain. Cost is a major reason why EEG still predominates in the field.
EEG Rhythms EEG signals vary dramatically over the course of a day and often correlate with particular states of behavior (e.g., level of attentiveness or sleeping) and pathologies (e.g., seizures). The main EEG rhythms (top) are categorized by their frequency range, and each range is name after a Greek letter. Epileptic discharges (bottom) are discrete events with complex morphology (often triphasic). 50uV Functions: connect/disconnect the cortex from sensory input bind percepts across cortex byproduct of interconnected circuits Epileptic seizure
Synchronous EEG Rhythms 1 Synchronous activity across a large set of cortical neurons can be produced in one of two fundamental ways (usually a combination): led by a central pacemaker (predominantly the thalamus) collective behavior among the cortical cells themselves Many different circuits of neurons can generate rhythmic activity. One common circuit consists of a source of constant excitatory input, feedback connections and synaptic excitation and inhibition. If rhythmic activity is generated in thalamus, then it acts as a pacemaker for cortex; if it arises in cortex, then collective behavior.
Synchronous EEG Rhythms 2 Evidence suggests that higher frequency waves in EEGs signals (e.g., beta) emerge from activity in cortex itself (perhaps due to different sets of inputs on the apical and basal dendrites of pyramidal cells), whereas lower frequency waves (e.g., delta) originate in thalamus. Association fibers Delta waves in individual thalamic neurons are created by an interplay of intrinsic voltage-gated channels (hyperpolarization-activated cation I h and low-threshold calcium I T ); the activity of each cell becomes synchronized with other cells via collective mechanisms. -60
Circadian Rhythms 1 Daily cycles of light and dark Schedules of circadian rhythms vary among species Most physiological and biochemical processes in body rise and fall with daily rhythms.
Circadian Rhythms 2 If daylight and darkness cycles are removed, circadian rhythms continue (called free-running rhythms) biological origin Free running rhythms are slow in humans; that is, about 25 hours long Brain clocks require occasional resetting Zeitgebers: environmental cues that entrain circadian cycles (primary cue: sunlight)
Internal Circadian Clock Suprachiasmatic nucleus (SCN) located in hypothalamus = sleep-wake circadian clock Lesions do not reduce sleep time, but they abolish its periodicity. Exhibits electrical, metabolic, and biochemical activity that can be entrained by the light dark cycle Transplant SCN, transplant sleep wake cycle Intact SCN produces rhythmic message: SCN cell firing rate varies with circadian rhythm ventrolateral preoptic optic chiasm paraventricular nucleus VLPO hypothalamus Visual input necessary to entrain sleep cycles to night
Visual Input to SCN Evidence suggests that axons from retinal ganglion cells synapse directly on the dendrites of SCN neurons (the retinohypothalamic tract). Inputs to the SCN come from special retinal ganglion cells that are themselves photosensitive (2%; not activated by rods or cones). The ganglion cells express melanopsin and are slowly excited by light. Roughly 10% of blind people lack these cells, and thus have freerunning sleep-wake cycles.
SCN Mechanisms 1 How do neurons of the SCN keep time? Isolation experiments, wherein SCN neurons are removed from the brain and separated from each other, reveal that firing rates, glutamate utilization, and protein synthesis continue to vary with rhythms of 24 hours. Data suggests that the rhythm is a molecular cycle based on gene expression. Individual SCN neurons express independently phased circadian rhythms. The nature of the neuronneuron coupling is poorly understood, but internal coupling (gap junctions; astrocytes?) generates a coherent output signal.
SCN Mechanisms 2 The molecular clock used in humans is similar to those used in mice, fruit flies and even mold. Clock genes include clock, period (per) cryptochrome (cry) The core circadian clock is formed by the positive and negative limbs of a transcriptional translational feedback loop (Takahashi 1998). In the positive limb, BMAL1 and CLOCK form heterodimers and activate the transcription of Per and Cry. PER and CRY proteins repress their own transcription by inhibiting CLOCK- BMAL1 activity in the negative limb.
SCN Mechanisms 3 Little is known how the molecular clockwork drives rhythms in neural activity of SCN neurons. Multiple mechanisms have been proposed.
Master Clock Research has shown that all cells of the body have a circadian clock (driven by the same type of gene transcription-translation negative feedback loop). Different cell types have their own circadian rhythm. Under normal conditions, however, all clocks are under the master control of the SCN, via its control of multiple signaling pathways. For example, the SCN has a strong circadian influence on core body temperature; the pulse of cooling at night ensures that the clocks of all internal organs remain set to that of the SCN.
Summary Rhythms are ubiquitous in the vertebrate nervous system, and they span a wide range of frequencies: cortical: 500-1Hz ultradian: less than a day circadian: about a day infradian: longer than a day Rhythms may be intrinsic (internal oscillations) or extrinsic in nature (network-based) Rhythms may or may not correlate with behavior; the sleep-wake cycle is characterized by many different rhythms.