Sensory pathways

Basal ganglia pathways

• The basal ganglia receive inputs from the cerebral cortex and send outputs back to it.
• These outputs influence motor function through two main pathways: the direct pathway (facilitates movement) and the indirect pathway (inhibits movement).
• Both pathways rely on excitatory glutamate signals from the cortex.

Dopamine from the substantia nigra pars compacta binds to D1 receptors to activate the direct pathway and to D2 receptors to suppress the indirect pathway, ultimately promoting movement.

Direct pathway

• Excitation from cortex: Cortical areas (primary and premotor) release glutamate, stimulating substance P-containing GABA neurons in the striatum (especially the putamen).
• Inhibiting the inhibitor: These GABA neurons inhibit GABAergic neurons in the internal globus pallidus. Because pallidal neurons are normally inhibitory, reducing their activity disinhibits the thalamic VA/VL nuclei.
• Thalamic activation: Freed from inhibition, the VA/VL nuclei send excitatory signals to the motor cortex, facilitating movement.
• Nigrostriatal support: Dopaminergic neurons from the substantia nigra project to the striatum. By acting on D1 receptors, dopamine enhances the direct pathway’s net excitatory effect on movement.

Indirect pathway

• Excitation from cortex: Glutamate from the cortex stimulates enkephalin-containing GABA neurons in the striatum.
• Double inhibition and subthalamic activation: These striatal neurons inhibit GABA neurons in the external globus pallidus. This increases activity of the subthalamic nucleus because the external globus pallidus normally inhibits it.
• Thalamic suppression: The subthalamic nucleus excites GABAergic neurons in the internal globus pallidus, increasing inhibition of the VA/VL nuclei in the thalamus and decreasing motor cortex activity.
• Neurotransmitters: Cholinergic neurons in the striatum further potentiate the indirect pathway, while nigrostriatal dopamine (D2 receptors) suppresses this pathway.

Reticular Activating System (RAS)

• The RAS is a network of brainstem neurons that project to the cortex through the thalamus and hypothalamus, regulating arousal and wakefulness.
• Its ascending fibers form the ascending reticular system, while its descending fibers (reticulospinal tract) modulate muscle tone, balance, and posture.
• Lesions can cause disorders such as narcolepsy or excessive sleepiness. PTSD may involve hyperactivity in the RAS.

Key nuclei and neurotransmitters in RAS:

• Locus coeruleus: Releases norepinephrine; active during wakefulness and slow-wave sleep.
• Dorsal raphe nucleus: Releases serotonin; also most active in waking and slow-wave sleep.
• Pedunculopontine nucleus: Uses acetylcholine and glutamate, essential for wakefulness and REM sleep.

Sleep physiology

Sleep alternates between non-rapid eye movement (NREM) and rapid eye movement (REM) stages about every ~90 minutes. Across the night, NREM time decreases and REM time increases.

1. NREM sleep

   • Awake EEG: Beta waves (high frequency, low voltage).
   • Eyes closed (still awake): Alpha waves (higher voltage).
   • Onset of NREM: Induced by GABA from the hypothalamic preoptic area and serotonin from raphe nuclei.
   • Stages I-IV: Progress from low-frequency theta waves (stage I) to sleep spindles and K complexes (stage II), then to slow, high-voltage delta waves (stages III-IV, with IV considered deep sleep). Muscle tone is reduced but not absent; blood pressure and heart rate decrease.

2. REM sleep (paradoxical sleep)

   • EEG: Resembles awake patterns (desynchronized or “sawtooth” waves).
   • Induction: Driven by cholinergic neurons in the ascending arousal system.
   • Features: Rapid eye movements, muscle atonia, pupil constriction, and fluctuations in vital signs. NE and serotonin neurons terminate REM, transitioning to NREM.

• Age-related changes:
  • Newborns spend ~50% of their sleep in REM; young adults ~25%; elderly significantly less.
  • Overall sleep time shortens with advanced age, with frequent awakenings and less stage IV/deep sleep.

These processes highlight how neural circuits and neurotransmitters coordinate motor regulation, arousal, and sleep to fine-tune bodily function.