Selection Flashcards
(42 cards)
What are the evolutionary problems the brain is trying to solve?
Survival and Reproduction
Specific functional system
one whose effects can be traced to a distinct location.
Example of a system with a specific function
The superior colliculus: Visual information is received from the retina, and processed by a somatotopic map, which directly influences eye movement
Generic function system
structures with repeating microarchitecture that process information from regions that perform widely different functions. All systems with a general function consist of reciprocal connects (re-entrant loops) with other regions.
Example of a system with a general function
the cerebellum
- has re-entrant loops with sensorimotor, cognitive, and motivational structures which allow the calibration and refinement of movement.
- It also possesses a repeated microarchitecture whereby the basic structural organisation is uniform across the cerebellum, despite having differing input/outputs.
What are two broad generic functions provided by the basal ganglia
- selection of the most appropriate movement, sensation, idea, emotion, etc… in a given situation based on previous experience
- reinforcement learning, whereby strategies are learnt that maximise the chance of a successful outcome in a given situation
How is the architecture of the basal ganglia relevant to its different functions?
The basal ganglia is functionally separated:
- Medial/Anterior = Limbic (NA/Caudate)
- Central = Associative (central striatum)
- Lateral/Posterior = Sensorimotor (putamen)
What are the major cell types/compositions within the striatum?
- 97% MSNs (medium spiny neurons): only cell type that projects out of the striatum.
- > 1% Cholinergic interneurons: receive thalamic and some cortical inputs and have a great influence on the function of the basal ganglia
- GABAergic interneurons
- VTA/SNpc dopaminergic neurons
What do the functional regions of the BG differ in?
o External inputs (cortex, limbic system, brainstem)
o Input functions (motivation, mood, cognition, sensorimotor)
Why is a brain area tasked with selection so important?
Our brain needs to address competing motivations (food, escape, fluid balance, pleasure) with the single set of muscles. Having a region specialised for selection allows relative importance of each motivation in order to determine which actions are executed.
Describe the disinhibitory loop of the BG
- The cortex has excitatory connections onto the MSNs of the striatum.
- MSNs have inhibitory projections onto SNpr neurons.
- The SNpr neurons tonically inhibit the thalamus.
- The thalamus has excitatory connections with the cortex.
A phasic excitatory burst from the cortex results in increased inhibition of SNpr neurons by increased MSN activity, which disinhibits the thalamus, allowing it to excite the cortex.
Mutual inhibition
The increased stimulation of a MSN by the cortex results in inhibition of nearby MSNs, to allow selection of an output channel.
Reinforcement learning
Reinforcement learning describes how actions that maximise the likelihood of a successful outcome are likely to be selected for.
Describe two targets where reinforcement can bias selection
- Cortical excitability
- Corticostriatal plasticity
What does dopamine signal?
Dopamine acts to signal the difference between and expected outcome and the actual outcome.
Describe an experiment to test the two modes of dopamine release on corticostriatal plasticity.
Experiment
Set up: Obtain an ex vivo slice from the thalamus/cortex that contains the desired circuitry
+ Insert stimulating electrode into the cortex and dopaminergic cells, as well as recording electrode on the MSNs
1. Stimulate the cortex on its own to obtain the baseline post-synaptic potential in MSNs
2. Co-stimulate dopamine cells and glutaminergic cortical cells
(Do this tonically/phasically to represent the absence/presence of a reward)
3. Stimulate the cortex on its own to determine if post-synaptic potential has increased/decreased
What is the evidence that dopamine release reinforces actions?
Intracranial self-stimulation involves the insertion of a stimulating electrode into the substantia nigra of a rat. The stimulation can be activated by a lever press. Rats will press the lever until exhaustion/death, indicating that the lever press action has been reinforced (to a pathological degree)
What is the evidence that dopamine release mediates corticostriatal plasticity?
Co-stimulation of cortical glutaminergic and dopaminergic inputs onto MSNs results in an increased post-synaptic potential after co-stimulation comparative to before. The absence of phasic dopamine during cortical stimulation results in a decreased post-synaptic potential, indicative of long term depression.
Corticostriatal potentiation requires D1 receptors, as potentiation does not occur in presence of a D1 antagonist.
Greater corticostriatal plasticity correlated to faster learning.
Corticostriatal plasticity is initiated when, and only when, the stimulus meriting phasic dopamine occurs within 2 seconds of cortical activation.
Sub-cellular mechanism of corticostriatal LTP
Glutamate is released from the thalamus/cortex and binds to AMPA receptors on MSNs
- AMPA receptor activation leads to cation influx and depolarisation
- Depolarisation repels the Mg2+ in NMDA channels
- NMDA activation allows calcium influx
Dopamine is released, and binds to D1 receptors (facilitated by TAN pause)
- Activation of Gas, causing increase in cAMP
Downstream results
- AMPA phosphorylation, which increases their efficacy, as well as changes in gene transcription and membrane expression
Subcellular mechanism of LTD
Glutamate binds to AMPA receptors
- Cation influx
- Depolarisation
Activation of L-type voltage-dependent calcium channels
- TAN pause required, as ACh binds mAChR which inhibits L-type VGCC
- Calcium influx (+ lack of cAMP)
Endocannabinoid production
- endocannabinoid diffuses out and binds to pre-synaptic membrane
- decreases glutamate release
What is corticostriatal LTP?
A POST-SYNAPTIC process enabled by phasic DA action on D2 & glutamate release
What is corticostriatal LTD?
A PRE-SYNAPTIC process enabled by the presence of tonic dopamine and action on D2
Give 4 pieces of evidence that associate dopamine with reward
- Dopamine cells exhibit phasic bursts in response to rewarding or reward-predicting stimuli
- Dopamine release in response to rewarding stimuli has been released in the striatum through electrochemical recording with carbon fibre electrodes
- Stimulation of dopamine pathways is rewarding
(ICSS: Stimulating electrodes reinforced behaviour more the closer they were to dopamine cells) - D1 receptor antagonists reduce the effectiveness of rewards
(Shifts dose-response curve of reward-related lever-press behaviour to the right)
Electrochemistry (DA)
Implantation of a carbon fibre electrode containing an electric potential. When implanted in dopamine cells the electrical potential oxidises dopamine, allowing measurement of current.
