Lecture 16- Circadian Rhythms

Descending Motor Pathways

Major Descending Tracts

A. Lateral Pathways

  1. Corticospinal Tracts (Pyramidal System)

    • Lateral corticospinal tract

      • Origin: Motor and somatosensory cortex.

      • Function: Precise, skilled voluntary movement, especially of distal limbs (fine motor control).

  2. Rubrospinal Tract

    • Origin: Red nucleus (midbrain).

    • Function: Facilitates flexor muscles of the upper limbs, minor role in humans.

B. Ventromedial Pathways

  • Medial or ventromedial corticospinal tract

    • Origin: Motor cortex.

    • Function: Controls proximal and axial muscles for posture.

C. Tracts from Brain Stem

  1. Vestibulospinal

  2. Reticulospinal

  3. Tectospinal

Brain Stem Pathways

  1. Vestibulospinal Tracts

    • Function: Coordinates head and neck position with eye movements.

    • Functions: Facilitates extensor muscles, maintains balance and posture.

  2. Reticulospinal Tracts

    • Function: Facilitates extensor tone, posture, locomotion.

    • Controls antigravity muscles (those that maintain upright posture against gravity, such as extensors of the legs and back).

    • Integrates voluntary movement with posture and reflex activity to control gravity.

  3. Tectospinal Tract

    • Origin: Superior colliculus (midbrain).

    • Function: Reflexive head and eye movements in response to visual and auditory stimuli.

Basal Ganglia

Structures of the Basal Ganglia

  • Components:

    • VL nucleus of thalamus

    • Caudate nucleus

    • Striatum

    • Putamen

    • Globus pallidus

    • Substantia nigra

    • Subthalamic nucleus

Basal Ganglia Loop

  • Neural connections include Area 4, Area 6, Central M1, PMA, S1, Posterior parietal cortex, SMA, Area 5, Prefrontal Area 7 cortex, BG, and Th.

Facilitation of Movement

  • Mechanism:

    • VL thalamus excites SMA, but is usually inhibited by the GP.

    • This inhibition of VL inhibits movement.

    • When the putamen is excited by frontal cortex, it inhibits GP, releasing the VL thalamus from inhibition and exciting the SMA.

    • This process initiates movement.

Disorders of the Basal Ganglia

  1. Parkinson’s Disease

    • Degeneration of the substantia nigra increases activation of the globus pallidus, leading to hypokinesia.

  2. Huntington’s Disease

    • Degeneration of the striatum disinhibits the VL, leading to hyperkinesia.

Cerebellum

Cerebellum Loop

  • Involves Area 4, Area 6, Central M1, PMA, S1, Posterior parietal cortex, SMA, Area 5, Prefrontal Area 7 cortex, Th, and Cb.

Motor Learning

Inputs to Purkinje Cells

  • Parallel fibers: 100,000 per Purkinje cell; produce action potentials in Purkinje cell.

Outputs

  • Action potentials in Purkinje cells are sent to motor cortex.

  • Climbing fibers: 1 per Purkinje cell; activated by errors.

  • Inferior olive indicates error detection.

  • Deep cerebellar nuclei is the output of the cerebellum.

Mechanism of Learning

  • Parallel fibers provide information about the current state of muscles, trajectory of the tennis ball, etc.

  • Purkinje cells gather that info and generate action potentials to make the appropriate swing.

  • Activation of the climbing fiber represents that a motor error has occurred.

  • A climbing fiber changes the properties of the Purkinje cell (plasticity) leading to improved motor coordination in subsequent attempts.

Biorhythms

  • Definition: Biorhythms are natural, repeating cycles in biological processes that help organisms adapt to predictable changes in the environment.

  • True Biological Rhythms: Self-sustaining and endogenous to the organism.

Circadian Rhythms and Non-Daily Periodicity

Types of Biorhythms

  1. Ultradian: Less than 1 day (e.g., feeding, breathing, REM/NREM cycles).

  2. Infradian: Over many days (e.g., reproductive cycle).

  3. Circannual: Yearly (e.g., mating, migration, hibernation).

    • Examples:

      • Seasonal breeding (e.g., deer mating in fall).

      • Molting/ coat changes (e.g., winter vs. summer fur).

Circadian Basics

Circadian Rhythm

  • Period: Approximately 24 hour period.

  • Self-sustaining and entrained by zeitgeber (usually light).

  • Definition of Zeitgeber: Environmental or exogenous cue that sets the internal ‘clock’.

  • Free Running: Occurs without zeitgebers.

Circadian Rhythms of Sleep and Wakefulness

  • Graph Explanation:

    • Daily plot of a specific person's sleep/wake cycles, where solid lines indicate sleep and dashed lines indicate wakefulness.

    • The triangle indicates the point of lowest body temperature.

    • After exposure to natural light/dark cycles, the individual maintained stable sleep/wake cycles but extended to 25 hours in absence of light cues.

    • The lowest body temperature shifted from the end of the sleep period to the beginning over time.

Additional Circadian Observations

  • Hamster Study:

    1. Device Monitoring Activity: A running wheel in a hamster's cage recorded activity.

    2. Activity Record: Shows hamster activity starting shortly before the dark phase and continuing throughout the dark period.

    3. Light Shifts: Alteration in light timing resulted in hamster phase shift of activity.

    4. Constant Dim Light: In continuous dim light, the hamster's activity showed a few minutes’ delay each day, indicating a free-running rhythm.

Daily Patterns of Physiological and Metabolic Activity

  • Circadian patterns observed in sleep/wake cycles, body temperature, hormones, and kidney functions, illustrating the ubiquity of circadian rhythms in physiological functions.

  • Notable example: cortisol follows a circadian pattern.

Key Features of Circadian Rhythms

  • Biological Cycles: Repeat approximately every 24 hours.

  • Endogenous Rhythm: Generated internally even without external cues, but synchronized by the environment.

  • Zeitgebers: Light is the most potent cue but can also include feeding times, temperature, and social activities.

  • Systems Involved: Circadian control extends beyond sleep/wake cycles to include hormone release (e.g., cortisol, melatonin), body temperature regulation, digestion, and gene expression across various cells.

Suprachiasmatic Nucleus (SCN)

Functions and Characteristics

  • Lesions can disrupt circadian rhythm.

  • Isolated SCN maintains a rhythm.

  • Transplantation of SCN can restore rhythm in animals with SCN lesions.

  • Neurons function as oscillators even in cell culture settings.

  • Circadian patterns can emerge in fetuses before synapses form.

Examples of SCN Functionality

  • Circadian rhythm in hamsters was disrupted by SCN lesions, indicated by random activity patterns in continuous dim light.

Retinohypothalamic Pathway in Mammals

Components of the Pathway

  • Specialized retinal ganglion cells with melanopsin project to the SCN via the retinohypothalamic tract.

  • Regular visual cells (rods and cones) provide form vision.

SCN Influence on Biological Rhythms

  • SCN employs neural pathways to influence other hypothalamic nuclei, regulating various systems and behaviors.

SCN and Pineal Gland Interactions

  • Melatonin is secreted by the pineal gland in response to signals from the SCN.

    • During darkness: SCN stimulates melatonin release, promoting sleepiness.

    • During daylight: Light inhibits this pathway, leading to decreased melatonin levels and thus promoting wakefulness.

Genetic Basis of Circadian Rhythm

Insights from Drosophila

  • Short-life span, easily manipulated in labs, small genomes help identify mutants with abnormal circadian cycles.

  • Identifying which genes differ helps bridge our understanding of circadian genetics.

The Drosophila Clock

  1. Per Gene: First clock gene cloned, regulating circadian oscillation of mRNA and protein levels.

  2. Tim Gene: Second gene that influences rhythmicity.

Genetic Process of 24h Rhythm Generation

  1. Daytime Activation: CLK and CYC form a complex activating transcription of per and tim genes.

  2. Protein Accumulation: PER and TIM proteins build up in the cytoplasm during the day.

  3. Nighttime Inhibition: PER-TIM complexes inhibit CLK-CYC, shutting down their own transcription.

  4. Negative Feedback Loop: Reduced mRNA leads to eventual degradation of PER and TIM proteins.

  5. Cycle Reset: As degradation occurs, CLK-CYC resumes activity, restarting the cycle.

  6. Light Entrainment: CRYPTOCHROME (CRY) detects blue light, triggers TIM degradation and resets the clock.

  7. Outcome: The feedback loop results in a ~24-hour circadian rhythm governing behavior and physiology.

Suprachiasmatic nucleus (SCN) in Mammals

  • In mammals, transcription factors are CLOCK and BMAL1.

  • Specialized retinal ganglion cells (with melanopsin) send direct signals to the SCN, which coordinates hormonal and autonomic outputs to regulate body rhythms.

  • Melanopsin in mammals and Drosophila CRY are analogous in function concerning light responsiveness but differ genetically.