Neuroscience final

Basal Ganglia I

Anatomy and ciruitry

-Deep brain structures

Composed of

  • Corpus Striatum

    • caudate nucleus

    • putamen

  • Globus Pallidus ( internal and external)

  • Sunthalamic nucleus

  • substantia nigra

    • pars compacta

    • pars reticulata

Striatal complexity

  • Side loop

  • odulate info from

    • Cortex→ motor and emotional

  • Loses function in disease or injury, leading to impaired movement and emotional regulation.

Neurons of the striatum

  • Medium spiny neurons (MSN) - 96%

    • neurins in caudate and putamen

  • Large dendritic trees to receive large aounts of info

  • Receive input from

    • Cerebral cortex via axons of pyrimidial neurons

    • Local interneurons in striatum, thalamus, and brainstem nuclei

  • Various points of contact on cell

    • Cortical neurons contact distal dendrites

    • other pathway contacts on shaft of dendrite colse to cell body

    • selectively modulate cortical input

INput to the basal ganglia ( Afferent pathways)

  • input (Afferent) → basal gnglia

  • cerebral cortex is largest source of inut

    • mostly from frontal and parietal lobes

  • terminate in striaum ( caudate and putamen)

  • corticostriatal pathway

    • prohections from subcortical white matter → striatum

  • imput forns glutamatergic ( excitatory) synapse in MSN in Striatum

  • Caudate receives input from

    • Motor Areas in frontal lobe that allow our eyes to move

    • association cortices that receive sensory input from thalamic nuclei and sensory cortices (somatosensory)

  • Putamen receives input from:

    • Primary and premotor cortices in frontal lobe

    • sensory cortices in parietal lobe

    • high order visual cortices

Striatum and Movement

  • MSN have little spontaneous activity

  • firing associated when we move

    • precedes actual movement

  • Putamen: associated with limb and trunk movements

  • Caudate: Associated with eye movements

  • Activity in striatum may assist in decision to move towards a target

    • some Striatal neuros fire according to the destination of the movement

Internal Pathways

  • Caudate and putamen project → globus pallidus and substantia nigra ( pars reticulata)

    • GABAergic ( inhibitory) connection

  • Like striatum, projections terminate in “ bands”

    • each band has a similar source of neurons from striatum

Efferent pathway (output)

  • GLobus Pallidus internal segment

    • Projects to thalamus ( ventral anterior and ventral lateral nuclei)

Thalamic nuclei project →motor areas of the cortex

  • Substantia Nigra ( pars reticulata)

    • Projects to superior colliculus (eye movement/ orienting visual gaze)

    • Minor projections→ thalamus →frontal eye fields ( prefrontal cortex)

  • Projections from the globus pallidus inferior and substantia nigra are GABAergic

  • High levels of spontaneous activity

    • inhibits unwanted movement by blocking the thalamus and superior colliculus

  • Activation of striatal neurons inhibits this pathway. removing inhibition on the thalamus and superior colliculus

    • This is called Disinhibition

    • allows movement to occur

INhibiton

Striatum: A is at rest

Globus pallidus: B is tonically active THEREBY…

VA/VL complex of thalamus: C is inhibited bc of B

Upper Motor neuron in cortex: So there is no excitation of D


Excitation

Striatum: A is transiently excited

Globus pallidus: B is transiently excited

VA/VL COmplex of thalamus: C is disinhibited; other inputs can excite it


Example of basal ganglia control

  • Substantia nigra pars reticulata projects to superior colliculus

    • contains upper motor neurons (UMN) the control Saccades

    • rapid, orienting movements of the eye

  • UMNs tonically inhibited by substantia nigra during visual fixation. This inhibition allows for the smooth pursuit of visual stimuli without involuntary saccadic movements.

  • bfore saccade, tonic discharge drops sharply

    • disinhibits UMNs so thecan produce movement

    • result of cortex exciting striatal neurons

Functions of Basal Ganglia

  • Facilitate motor programs that express movement

  • suppress competing or unnecesary motor programa that may interfere

  • two pathway

    • direct pathway: net effect is to excite motor cortex; selects motor program

      • projections from MSN of striatum → internal globus padillus (GPi)

      • Activation of striatal neurons inhibits the inhibitory effect of GPi; double negative=positive

    • Indirect: net effect is to inhibit the cortex

      • dampens unwanted motor programs to prevent unwanted movements

      • inreases tonic inhibition of tha;amus by internal GPi ans sub.nig pars reticulata

      • different set of MSN project from striarum to ext. GPi ( inhibitory)

      • Ext. GPi smeds projections to internal segment of GPi and Subthalamic nucleus

      • Subnucleus excites internal segment of globus pallidus via glutamatergic action

OVERVIEW:

Direct: promotes movement D1 receptors

  1. cortex excites striatum

  2. striatum inhibits the GPi

  3. GPi normally inhibits the thalamus, but now its less active

  4. The thalamus is Disinhibited b→ sends more excitatory signals to the motor cortex

Indirect Pathway ( inhibits movement)

  1. cortex excites striatum

  2. striatum inhibits the GPe

  3. GPe normally inhibits the subthalamic nucleus (STN) , bit now its less active

  4. STN is disinhibitied and excited the GPi

  5. GPi increases inhibition of the tha;amus, sending less input to the motor cortex

  6. movement is reduced or stopped

Balamce of pathways

  • inderect pathway antagonizes direct pathway

  • balance is needed for proper execution of movements

  • individual axons from striatum to GPi synapse densly on particular neurons

    • direct pathway can “ focus” imput on particular area for output

  • Subthalamic neurons synapse more widely with GPi

    • indirect pathway has a broader influence on output

Basal ganglia Plasticity

Recall

  • Nt synthesis and metabolism

  • ask abt review

Synaptic plasticity overview

  • Short terms ( ms to mins)

    • facilitation depression

  • paired pulse

  • post-tetanic potentiation

  • Long term (mins to hrs)

    • Long term poterntioation

    • long term depression

  • every synapse has potential for plasticity

Shprt term synaptic plasticity

Facilitation:

Augmentation:

potentiation:

  • all presynaptic

  • increase in number of transmitter quanta without changr in quantal size

Animal models of PD

Toxin based

  • MPTP

  • 6-Hydroxydopamine: form of DA that selectively destroys dopaminergic neurons, commonly used in research to model Parkinson's Disease.

  • Rotenone ( Hepbicide + pesticide): destroys neurons within the striatum and induces parkinsons sysmptoms

  • Paraquat( herbicide)

  • Amphetamine derivatives

  • Genetic mutationMice VERY IMPORTANT

    • dominant( alpha-synuclein, LRRK2 Mutants)

    • Recessive (PINK1, DJ-1 Knockouts)

  • Synaptic plasticity is dependent on the

    • Pathways ( e.g., corticostriatal vs. Thalamo-striatal vs. Thalamo nigral) and synapses

    • frequency of stimulation

    • order of stimulation ( cortex → striatum OR striatum → cortex)

    • transmitters and modulators present

Cortico-striatal LTD( direct pathway): This is a process where prolonged low-frequency stimulation of cortical inputs to the striatum leads to a long-term decrease in synaptic strength, mediated by endocannabinoids and other neuromodulators.

  • prevents glutumate from acting onpostsynaptic receptors, thereby reducing excitatory signaling and contributing to the overall decrease in synaptic efficacy.

  • D1 receptors

Cortico-striatal LTD (Indirect Pathway):

  • D2 receptors

  • both wayways are a result of postsynaptic and presynaptic factors

Striatal synaptic plasticity

  • Normal healthy cortical inputs to:

    • MSN in Direct pathway to shot LTP then LTP

    • MSN in indirect pathway show LTD then LTP

  • Parkinsins disease corical inputs

    • MSN in direct pathway only show LTD

    • MSN in Indirect pathway only show LTP

  • All synapses are capable of plasticity

  • What abt interneurons?

    • bla bla

    • i hope she goes backa slide 1:36

Basal ganglia Plasticity

Subthalamic Nucleus

  • spontaneously active

  • sets excitatory tone for outputs (GPi)

  • shows LTP and LTD

    • D2,

Substania NIgra

  • LTD and LTD at SNpc

  • LTD at SNpr

parkinson’s disease- DA loss changes striatal synaptic plasticity


Summary

  • there are several forms of synaptic plasticity that can last from seconds to days

  • most brief form of presynaptic and longer forms are post-synaptic, require calcium and protein synthesis

  • LTP and LTD can occur in Multiple synapses in the basal ganglia and cortex, influencing motor control and learning processes, highlighting the importance of these mechanisms in both normal brain function and various neurological disorders.

  • FINISH THIS FROM 4/23 VIDEOOOO



Speech anad language

  • Localized brain regions for language in temporal and frontal association cortices

  • Lateralization of language functions

  • Left sphere predominant

    • links btwn speech sounds and thier meaning

    • motor commands to organize meaningful speech production

  • Right Hemisphere important for emotional and affective qualities of speech

    • tone

    • pitch

  • Main concern for crtical areas of language is using symbols for comunication

    • essential fucntion is symbpl representation FINISH

  • Regardles of mode of expression, language is about symoblic representation

    • Grammar- setif rules for using symbols

    • syntax- orderinf symbols to create useful meaning

    • prosody- emotional meanig through variations in rhythm, stress, and tone

Cortical Language Areas

  • We process language independently from the motor pathways for speech

    • Compromised ability to move larynx, pharynx, mouth does NOT abolish ablity to use kanguage to communicate

  • Brocas area: in the “back” of the Frontal lobe (left)

    • ability to effectively produce language

  • Wernicke’s area- Top of th left temporal lobe

    • responsible for language comprehension, allowing individuals to understand spoken and written language, and to formulate meaningful sentences.

COrtical centers and aphasias

Aphasia: Syndromes that diminish or abolish ability to comprehend or produce language

  • Lose ability to recognize or employ words correctly

Three categories:

  • motor or expressive( Brocas Aphasia)

    • Damage to Brocas area

    • cannot produce language effectively

  • sensory receptive ( Wernicke’s Area)

    • damage to left temporal lobe

    • difficulty understanding splen languade

    • produce souns but irrelevent answers

  • conduction

    • Lesions to pathways connecting relevant temporal and frontal areas

    • inability to produce appropriate responses

    • response might not make snese although they understand you

Modulation of Basal Ganglia

  • Widespread projections from Snpc → striatal neurons

  • dopamenrigic system: Dopamine receptors on shaft of dendrite of MSN that project to GPi, influencing the direct and indirect pathways involved in motor control and reward processing.

  • Effect of DA release is dependent on receptor subtype on striatal neurons

    • D1receptors- excitatory effect

    • D2 receptors- inhibitory effect

Dopamine pathways in the CNS

“ Dopaminergic” neurons synthesize and secrete the NT dopamine

  • Derived from L-tyrosine → L-DOPA → Dopamine

  • four pathways

    • mesolimbic: VTA→NaC & basal ganglia

    • Mesocortical: VTA→ PFC

    • nigrostriatal Substabtia nigra → Striatum ( Loss of specific neuron sin extrapyrimidal system leading to motor abnormalities like Parkinson’s disease)

    • Tuberoinfundibula: arcuate nucleus → Pituitary gland (involved in hormone regulation, impacting reproductive functions).

  • Direct pathway striatal neurons have D1 receptors

    • excite neurons

    • net excititatory effect on pathway ( excite cortex)

  • Indirect pathway neurons have D2 receptors

    • inhibit neurons

Ah, the basal ganglia—one of those topics that seems complex at first but makes a lot of sense once you break down the pathways! Let’s cover both the direct and indirect pathways in a normal, healthy person.

🧠 Basal Ganglia Overview

The basal ganglia are involved in:

  • Motor control (initiating/suppressing movement)

  • Motor learning/habit formation

  • Regulating voluntary movement

Key structures:

  • Striatum (caudate + putamen)

  • Globus pallidus (internal [GPi] and external [GPe])

  • Subthalamic nucleus (STN)

  • Substantia nigra (pars compacta [SNc] & pars reticulata [SNr])

  • Thalamus

⚡ Direct Pathway (GO Pathway)

Facilitates movement
“Turn the movement ON!”

  1. Cortex → releases glutamate to stimulate the striatum.

  2. Striatum → releases GABA to inhibit GPi/SNr (which are normally inhibitory).

  3. Inhibition of GPi/SNr = less inhibition of the thalamus (disinhibition).

  4. Thalamus becomes more active → excites the motor cortex → movement is promoted.

🟢 Dopamine (from SNc) stimulates the direct pathway via D1 receptors, further promoting movement.

🚫 Indirect Pathway (NO-GO Pathway)

Inhibits movement
“Turn the movement OFF!”

  1. Cortex → stimulates striatum with glutamate.

  2. Striatum → inhibits GPe with GABA.

  3. Inhibition of GPe → less inhibition of the subthalamic nucleus (STN).

  4. STN becomes more active → stimulates GPi/SNr.

  5. GPi/SNr strongly inhibits the thalamus → reducing motor cortex stimulation → movement is suppressed.

🔴 Dopamine (from SNc) inhibits the indirect pathway via D2 receptors, reducing movement suppression.

🎯 Key Points for a Healthy Person:

  • Balance between the direct and indirect pathways allows for smooth, controlled movements.

  • Dopamine from the substantia nigra pars compacta (SNc) modulates both pathways:

    • Stimulates direct pathway (via D1) → promotes movement.

    • Inhibits indirect pathway (via D2) → reduces movement suppression.

  • Dysfunction in either pathway can lead to movement disorders (e.g., Parkinson’s, Huntington’s).

🔄 Flow Summary

Pathway

Function

Key Neurotransmitters

Receptors

Effect on Movement

Direct

Movement initiation (GO)

Glutamate, GABA, Dopamine

D1 (excitatory)

Facilitates movement

Indirect

Movement inhibition (NO-GO)

Glutamate, GABA, Dopamine

D2 (inhibitory)

Suppresses movement

🌟 Extra Tips:

  • Think of the direct pathway as hitting the gas and the indirect pathway as pressing the brakes.

  • Dopamine balances both to keep movement smooth.


Basal ganglia movement disorders

Parkingsons Disease

✅ Cause:

  • Loss of dopaminergic neurons in the substantia nigra pars compacta (SNc)

🔄 What Happens?

  • ↓ Dopamine → less stimulation of D1 receptors on the direct pathway

  • ↓ Dopamine → less inhibition of D2 receptors on the indirect pathway
    → Less movement promotion + more movement suppression

🧩 Result:

  • Underactive direct pathway

  • Overactive indirect pathway

🔵 Huntington’s Disease (HD)

✅ Cause:

  • Autosomal dominant mutation in the HTT gene (CAG repeat expansion)

  • Leads to death of medium spiny neurons in the striatum, especially those in the indirect pathway

🔄 What Happens?

  • ↓ Indirect pathway activity

  • The GPe is less inhibited → STN is less active → GPi is less active
    → Less inhibition of the thalamus → Too much movement

🧩 Result:

  • Overactive direct pathway (relatively speaking)

  • Underactive indirect pathway