Mapping Flashcards
Describe the layout of the visual system regarding retinal ganglion cells and the tectum
Anterior retinal ganglion cells lie closest to the nose and send their axons to the posterior tectum
Posterior retinal ganglion neurons send their axons to the anterior tectum
Same applies with dorsal and ventral
How is it that the tectal neurons know which way to go?
A gradient of signaling molecules guides tectal neurons’ direction.
The ‘Stripe assay’ demonstrated:
Cells from the posterior tectum produce a non-permissive factor that repels temporal retinal axons.
The non-permissive factors are ephrins.
Ephrins A2 + A5
Ephrin receptors are expressed in the retina in a counter gradient, creating directional guidance.
This interaction forms stripes that guide the axons’ growth.
How is this related to mapping and what happens in KO’s?
The combination of ephrin gradients in the tectum and receptor gradients in the retina acts like a map.
- This ensures axons grow to their proper locations, forming organized connections between the retina and the tectum.
When you KO the ephrins you get a disruption of the map with the stripes
How is competition involved in mapping?
Initial Growth: Axons first extend throughout the tectum.
Ephrin Gradient: Guides branching and synaptogenesis, restricting axons to specific regions.
Competition: Axons compete for synaptic partners via electrical activity; weaker synapses are eliminated.
Result: Ensures precise and efficient neural connections.
How can electrical activity modulate response to guidance cues?
- Electrically stimulating the axon can get it to turn towards a lower concentration of an attractant molecule (netrin)
- Opposite situation has also been seen with inhibitory molecules , if you stimulate the axons these repellent molecules become attractive
- The fact it can be reversed implies it is going through the cGAMP and cAMP stage which is what is happening
- also found more pulses= more stable Ca2+ elevation
What is meant by the refinement of connections?
- Activity dependent
- Neighbouring cells initially make contacts over large overlapping areas of the tectum
- At later stages it becomes more precise
- This refinement depends on competition
- Seen in ocular dominance columns
What happens if you block the activity of one eye in an ocular dominance column?
you see the activity of the working eye spreads out among the cortex because there is no competition anymore
What happens when two cells fire at the same time?
Hebbian rule: The mechanism of synapse elimination involves the localised release of neurotrophic factors which is thought to be enhanced when two cells fire at the same time
What is the issue with assuming the synaptic activity contributes to mapping?
Visual system mapping occurs before there is light so where does the electrical activity come from?
How does visual mapping occur with no light?
Spontaneous Retinal Activity:
The retina becomes spontaneously active as axons reach the tectum.
Neighboring retinal cells fire together, creating spatially coherent activity.
Role of Firing:
Simultaneous firing provides spatial information and a competitive advantage, strengthening synapses and refining the map.
Blocking Activity Disrupts Refinement:
- Sodium channel blockers prevent action potentials, disrupting map refinement.
- Blocking acetylcholine receptors using mutated receptors (no B2 subunit) also reduces refinement.
How is BDNF relevant to retinal electrical activity?
- Enhances retinal electrical activity results in BDNF+ upregulation
- BDNF promotes RGC axon branching but only in region where Eph-ephrin interactions are low
- You need an eph-ephrin interaction to occur but it needs to be at a low level
- Too much means branching does not form properly
How does mapping occur when RGC axons project on to the Lateral Geniculate Nucleus?
- LGN receives inputs from both eyes.
- Guidance of RGC axons to these layers is predetermined.
- Mapping of RGC axons onto the LGN is still topographic and is also set up using similar gradients of Ephrins (Feldheim et al., 1998)
How does receptor expression work in the olfactory system?
- 1000+ Olfactory Receptors: Each neuron expresses only one receptor type (part of the GPCR family).
- Complex Regulation: Ensures only one receptor is expressed per neuron.
- Dispersed Organisation: Receptors are distributed randomly across the nasal epithelium.
How do neurons connect to glomeruli in the olfactory system?
Convergence: Neurons expressing the same receptor synapse on a specific glomerulus.
Function: Each glomerulus receives input from neurons with one receptor type.
Evidence: RT mapping shows neurons of one receptor class converge on a single glomerulus.
How is the IRES technique used in olfactory research?
- Allows expression of a reporter gene (e.g., GFP) alongside an olfactory receptor to study neuron behavior.
- Tracks neurons expressing a specific receptor type to observe glomerulus targeting.
- Helps investigate how receptor expression affects axonal convergence onto glomeruli.
RT Mapping: Confirms neurons expressing the same receptor converge on a single glomerulus.
What determines where neurons detecting similar odorants go?
- Spatial relationship where glomeruli responding to related odorants are clustered in the olfactory bulb
- This is due to which olfactory receptor is expressed by the olfactory sensory neuron
- Coding regions have been switched around in the receptor genes, finding the sensory neurons went to different places
How does olfactory receptor activity determine guidance response state?
Activity-Independent Growth: Early axon guidance to the olfactory bulb (OB) does not rely on neuronal activity or odors.
Basal Signaling: Each olfactory receptor (OR) has characteristic basal activity, leading to similar cAMP levels in neurons expressing the same OR.
CREB Regulation: cAMP activates CREB, which regulates the expression of guidance cues like Robo/Slit. (Type 1 molecules)
Outcome: Basal OR activity (forming similar proteins) ensures axons expressing the same OR converge on the same glomerulus in the OB
What is meant in terms of the olfactory system as a continuous map?
- Axons entering OB are pre-sorted due to type 1 cue/receptor interactions which is activity independent
- Because they have similar levels of certain genes being expressed due to the basal signalling of cAMP etc. they go to the same place
- Cue expression switches with time (Robo/slit → semaphorin for e.g.) so that early entering axons then guide later entering axons
What is meant by a discrete map in terms of the olfactory system?
- Sorting in to glomeruli is activity-dependent
- Activity drives higher cAMP levels which turn on expression of type 2 molecule cues such as mutual repellants (Ephs, ephrins) and adhesion molecules
- These interactions sort axons expressing same ORs into groups to form the glomerulus
End up with discrete spatial segregation based on an early topographic map
Beyond the bulb, is there spatial organisation?
- Olfactory signals ar relayed from bulb to SC, LGN, and then cortex etc.
- Unlike the visual system, mitral cell axons projecting to the piriform cortex do not exhibit any spatial organisation
- Individual piriform cortex neurons respond to multiple structurally dissimilar odorants
How was it tested whether the piriform cortex was the site of olfactory learning?
- Smell –> behaviour, what regions are involved?
- Optogenetic activation using channelrhodopsin in naive unconditioned animals
What was the experimental strategy and results of testing the piriform cortex?
- Induce channelrhodopsin into PC neurons
- Stimulate with light , paired with an aversive/ appetitive stimulus in naive and conditioned animals
- Now, can the light alone elicit the response?
- Chr was introduced using viruses, either synapsin promoter or cre-lox system where gene is inverted, not deleted
- Photostimulation of Chr in piriform neurons was paired with a shock, animals exhibited flight behaviour to PhSt alone, but only when it was in the piriform neurons
How was it shown that ChR2 photo stimulation can also drive appetitive behaviours?
- Mice trained to take water in response to odorant, could be re-trained to respond instead to PhSt
- Male mice also could be trained to associate presence of a female with either an odour as the CS or with PhSt as the CS
How are piriform neurons plastic in their associative capability?
- Same set of ChR2-exppressing PC neurons can be retrained in either directions to elicit different behaviours
NONE OF THIS SHOWS REQUIREMENT, JUST ASSOCIATION as no KO have been done
Which parts of the brain are involved in odour recognition/response?
Piriform cortex- identifies odour
Amygdala - how pleasant it is
Hippocampus - recognise name
Neurons that react to the smell can also react to visual and linguistic cues e.g. the smell of liquorice, name and image
How do we explain innate smells?
- A small subset of odours elicit innate responses
e.g. trimethyl-thiazoline (TMT) from fox elicits fear (in mice!) - There are specific projections from OB to cortical amygdala that may be involved
