Basal Ganglia Structure and Function

Basal Ganglia

• A group of nuclei that act as a unified functional unit, closely associated with the cerebral cortex and corticospinal motor control system.
• Receives most input signals from the cerebral cortex and returns almost all output signals back to the cortex.

Basal Ganglia Structure

• Consists of four principal nuclei:
  • Striatum (input nucleus)
  • Globus pallidus (two separate nuclei: external and internal segments)
  • Subthalamic nucleus
  • Substantia nigra (two separate nuclei: pars compacta and pars reticulata)

Striatum

• Receiving afferent projections from the cerebral cortex
• Comprised of three subnuclei:
  • Caudate nucleus (participates in eye movement control and cognition)
  • Putamen (participates in control of limb and trunk movements)
  • Nucleus accumbens (participates in emotions)

Globus Pallidus

• Internal segment: one of the major output structures of the basal ganglia
• External segment: part of the intrinsic circuitry of the basal ganglia

Substantia Nigra

• Pars compacta: contains dopaminergic cells that project heavily to the striatum
• Pars reticulata: can be viewed as a single output structure with the internal segment of the globus pallidus

Subthalamic Nucleus

• Small nucleus situated between the thalamus and the substantia nigra
• Receives projections from the external segment of the globus pallidus, the cerebral cortex, thalamus, and brain stem
• Sends output to both segments of the globus pallidus and to the substantia nigra pars reticulata

Basal Ganglia Input

• Receives input from various cortical regions:
  • Parietal cortex (primary and secondary somatosensory information, secondary visual information)
  • Temporal cortex (secondary visual and auditory information)
  • Cingulate cortex (limbic and emotional status information)
  • Frontal cortex (primary and secondary motor information)
  • Prefrontal cortex

Cortico-Basal Ganglia-Thalamocortical Circuits

• Two important pathways through which striatal information reaches the globus pallidus (internal):
  • Direct pathway: striatal cells project directly to the globus pallidus (internal)
  • Indirect pathway: striatal cells project to the globus pallidus (external)
• The direct pathway increases the excitatory drive from the thalamus to the cortex, facilitating movement
• The indirect pathway decreases the excitatory drive from the thalamus to the cortex, inhibiting movement

Neurotransmitters in the Basal Ganglia

• Dopaminergic modulation: increases motor activity
• Cholinergic modulation: decreases motor activity by inhibiting striatal cells of the direct pathway and exciting striatal cells of the indirect pathway

Functions of Basal Ganglia

• Voluntary movement
• Postural control
• Control of muscle tone
• Role in arousal mechanism
• Speech
• Cognitive control of motor activity
• Planning and programming of movements
• Timing and scaling of intensity of movements
• Subconscious execution of some movements

Lesions of Basal Ganglia

• Globus pallidus: athetosis (spontaneous writing movements of the hand, arm, neck, and face)
• Putamen: chorea (flicking movements of the hands, face, and shoulders)
• Substantia nigra: Parkinson's disease (rigidity, tremor, and akinesia)
• Subthalamus: hemiballismus (sudden flailing movements of the entire limb)
• Caudate nucleus and putamen: Huntington's chorea (loss of GABA-containing neurons to the globus pallidus and substantia nigra)

Chemical Senses: Smell

• Smell (olfaction) and taste (gustation) are classified as visceral senses, physiologically related to each other.
• Smell receptors are chemoreceptors and extereceptors, stimulated by dissolved chemical molecules in mucus.

Olfactory Receptors

• Humans have approximately 350 different odorant receptors, belonging to the G protein-coupled receptor superfamily.
• Odorant receptors can distinguish between estimates of up to 30 million compounds.

Physiological Importance of Smell

• Smell plays a major role in finding direction, seeking prey, avoiding predators, and sexual attraction in lower animals.
• In humans, the sense of smell is less sensitive and less important in influencing behavior.

Olfactory Membrane and Cells

• The olfactory membrane lies in the superior part of the nasal cavity, with a surface area of about 2.4-5 cm2 in each nostril.
• There are 10 million-100 million bipolar olfactory neurons, with a lifespan of about 30-60 days, continuously replaced from a layer of basal stem cells.
• Each cell has 4-25 cilia, with olfactory cilia projections reaching into the mucus that coats the inner surface of the nasal cavity.

The Structure of the Olfactory System

• Bowman glands secrete mucus onto the surface of the olfactory membrane.
• Odorant molecules bind to olfactory receptors, activating adenyl cyclase, leading to depolarization.

Physiologic Factors for Olfactory Stimulation

• Substances must be volatile, slightly water-soluble, and slightly lipid-soluble to stimulate olfactory cells.

Olfactory System

• At each glomerulus, there are 25 mitral cells, 60 tufted cells, and 25,000 olfactory axons.
• The medial olfactory area, composed of nuclei in the midbasal portions of the brain, is associated with primitive responses to olfaction.

Abnormalities in Odor Detection

• Anosmia (inability to smell) and hyposmia (diminished olfactory sensitivity) can result from nasal congestion, polyps, damage to olfactory nerves, tumors, respiratory tract infections, and prolonged use of nasal decongestants.
• Hyperosmia (enhanced olfactory sensitivity) is less common, but can occur in pregnant women.
• Dysosmia (distorted sense of smell) can be caused by sinus infections, partial damage to olfactory nerves, and poor dental hygiene.

Chemical Senses: Taste

• Taste (gustation) and smell (olfaction) are classified as visceral senses and are physiologically closely related to each other.
• Taste receptors are chemoreceptors and exteroceptors that are stimulated by dissolved chemical molecules in saliva.

Taste and Smell Sensations

• Taste and smell sensations allow individuals to distinguish between estimates of up to 30 million compounds.
• Stimulation of the taste or smell receptors induces pleasurable or objectionable sensations, leading to seeking nutritionally useful food or avoiding potentially toxic substances.

Chemical Receptors in Taste Cells

• At least 13 probable chemical receptors have been identified in taste cells, including:
  • 2 sodium receptors
  • 2 potassium receptors
  • 2 sweet receptors
  • 2 bitter receptors
  • 1 chloride receptor
  • 1 adenosine receptor
  • 1 inosine receptor
  • 1 glutamate receptor
  • 1 hydrogen ion receptor

Primary Sensations of Taste

• Primary sensations of taste have been grouped into five general categories:
  • Sour
  • Salty
  • Sweet
  • Bitter
  • Umami (delicious)

Taste Substances

• Sour taste is caused by acids (H+ ions) and is triggered by the Epithelial sodium channels (ENaC) that allow protons to enter the cytoplasm.
• Salty taste is mediated by Na+ influx through amiloride-sensitive Na+ channels, with the main receptor being the epithelial sodium channel (ENaC).
• Bitter taste is associated with gustducin (a heterotrimeric G protein) receptor and is caused by different compounds, most of which are poisons.
• Sweet taste is triggered by sweet tastants, G protein (gustducin), and adenylyl cyclase, leading to the release of cAMP and depolarization.
• Umami taste is triggered by amino acids and is mediated by the activation of the metabolic glutamate receptors (mGluR4) in taste buds.

Threshold for Stimulation

• Sour: 0.0009 N HCl
• Salty: 0.01 M NaCl
• Sweet: 0.01 M Sucrose
• Bitter: 0.000008 M Quinine

Taste Buds

• Taste buds are composed of 50-100 modified epithelial cells (taste and supporting cells) with a diameter of 1/30 mm and a length of 1/16 mm.
• Microvilli provide receptor surface for taste.
• Adults have 3,000-10,000 taste buds on the surface of the tongue, with about 1,000 taste buds in the roof of the mouth and wall of the throat.

Location of Taste Buds

• Taste buds are located on:
  • Circumvallate papillae (V line on the surface of the posterior tongue)
  • Fungiform papillae (top side)
  • Foliate papillae
  • Palate
  • Tonsillar pillars
  • Epiglottis
  • Proximal esophagus

Distribution of Taste on the Tongue

• Salty and Sweet taste buds are located on the tip of the tongue.
• Sour taste buds are located on the lateral edges of the tongue.
• Bitter taste buds are located on the root of the tongue and soft palate.

Transmission of Taste Signals

• Signals from the anterior two-thirds of the tongue pass through the lingual nerve, chorda tympani, and facial nerve into the nucleus tractus solitarius (NTS).
• Signals from the circumvallate papillae and posterior regions of the mouth and throat are transmitted through the glossopharyngeal nerve into the NTS.
• Signals from the base of the tongue and pharyngeal region are transmitted into the NTS by way of the Vagus nerve.
• Signals from the NTS pass to the Ventral posterior nucleus of the thalamus and then to the Gustatory cortex.

Taste Reflexes

• From the NTS, many taste signals are transmitted to the superior and inferior salivatory nuclei.

Motor Functions of the Spinal Cord

• The spinal cord is not just a conduit for nerve fibers, but contains neuronal circuits for walking and various reflexes that can be activated and commanded by higher brain centers.
• The spinal cord is organized to transmit sensory information to higher centers and to elicit motor reflexes locally.

Anterior Motor Neurons

• Alpha motor neurons:
  • Give rise to large type A alpha fibers (~14 microns)
  • Stimulation can excite 3-100 extrafusal muscle fibers collectively called a motor unit
• Gamma motor neurons:
  • Give rise to smaller type A gamma fibers (~5 microns)
  • Stimulation excites intrafusal fibers, a special type of sensory receptor

Interneurons and Propriospinal Fibers

• Interneurons:
  • 30 times as many as anterior motor neurons
  • Small and very excitable
  • Comprise the neural circuitry for motor reflexes
• Propriospinal fibers:
  • Travel up and down the cord for 1-2 segments
  • Provide pathways for multisegmental reflexes

Sensory Receptors of the Muscle

• Muscle spindle:
  • Senses muscle length and change in length
• Golgi tendon organ:
  • Senses tendon tension and change in tension

The Muscle Spindle

• The center has no contractile elements and responds to stretch
• Ends have contractile elements
• Three types of fibers:
  • Primary (1a) afferents innervate all three fiber types
  • Secondary (Group II) afferents innervate static bag and chain fibers
  • Gamma motor neurons innervate the ends of intrafusal fibers

Response of the Muscle Spindle

• Static response:
  • When the center of the spindle is stretched slowly, the number of impulses generated by the primary and secondary endings increases in proportion to the degree of stretch
• Dynamic response:
  • When the center of the spindle is stretched rapidly, the number of impulses generated by the primary endings increases in proportion to the rate of change of length

Gamma Motor Nerves to the Spindle

• Divided into gamma s and gamma d, which innervate the contractile ends of the respective intrafusal fibers
• Contraction of the ends will stretch the middle of the fiber

Physiologic Function of the Muscle Spindle

• Comparator of length between the intrafusal and extrafusal muscle fiber
• Opposes a change in length of the muscle
• When the muscle is stretched, the spindle returns it to its original length, leading to the stretch reflex

The Stretch Reflex

• Opposes further stretch of the muscle
• Afferent impulses to the cord excite the alpha motor neuron, resulting in contraction of the muscle
• Sudden stretch of the muscle excites the muscle spindle

Changing Muscle Length

• Coactivation of alpha and gamma motor neurons causes contraction of the muscle and the ends of the spindle, resulting in a shortened spindle with an intact stretch response

Function of the Gamma System

• Controls the intensity of the stretch reflex
• Performs a damping function by adjusting sensitivity
• The spindle is normally tonically active as a result of input from higher brain centers

Clinical Application of the Stretch Reflex

• Knee jerk reflex:
  • Striking the patellar tendon with a hammer stretches the quadriceps muscle and initiates a stretch reflex
  • Can be done with almost any muscle
  • Index of the facilitation of the gamma efferents

Golgi Tendon Reflex

• Mediated by the Golgi tendon organ receptor located in the tendon
• Responds to tension
• Function is to equalize force among muscle fibers

Transmission of Stretch Information to Higher Centers

• Muscle spindle and Golgi tendon signals are transmitted to higher centers
• Informs the brain of the tension and stretch of the muscle
• Important for feedback control of motor activity

The Withdrawal Reflexes

• A painful stimulus causes the limb to automatically withdraw from the stimulus
• Neural pathways for reflex:
  • Nociceptor activation transmitted to the spinal cord
  • Synapses with pool of interneurons that diverge to the muscles for withdrawal, inhibit antagonist muscles, and activate reverberating circuits to prolong muscle contraction
• Duration of the after discharge depends on the strength of the stimulus

Crossed Extensor Reflex

• Painful stimulus elicits a flexor reflex in the affected limb and an extensor reflex in the opposite limb
• Extensor reflex begins 0.2-0.5 seconds after the painful stimulus
• Serves to push the body away from the stimulus and shift weight to the opposite limb