1.1.1 In addition to projections to the tectum (superior
colliculus), mammalian retinal ganglion cells (RGCs)
also project to the lateral geniculate nucleus (LGN),
which relays these inputs to the cortex:
188.8.131.52 Interestingly, the mapping of RGC axons onto the LGN is
also topographic and is set up using similar gradients of
184.108.40.206.1 (Feldheim et al., 1998,
Neuron, 21 1303)
220.127.116.11.2 Unlike the tectum, the LGN
receives inputs from both eyes
18.104.22.168.2.1 allows stereoscopic
vision to be integrated
22.214.171.124.2.2 Terminals from, say, the temporal retina of the left eye
(blue) are located in adjacent layers of the same region of
the LGN as those from the temporal right eye (red)
126.96.36.199.2.2.1 Guidance of RGC axons to
these layers is predetermined.
1.2 Olfactory system
1.2.1 How do you represent a
188.8.131.52 1000 receptors but each
neuron expresses only one!
184.108.40.206.1 “One neuron –
one OR” principle
220.127.116.11 Receptor expression dispersed in nasal epithelium, but
axons become organised in the olfactory bulb (OB)
18.104.22.168.1 How is this done?
22.214.171.124.1.1 Mapping from
epithelium to bulb
126.96.36.199.1.1.1 Critically different
from RT mapping:
188.8.131.52.1.1.2 Glomeruli responding
to related odorants
are clustered in OB
184.108.40.206.1.2 Receptor expression governs guidance
220.127.116.11.1.2.1 Receptor swap experiments demonstrate
that where axons go is determined by
which receptor is expressed.
18.104.22.168.1.2.2 OR activity determines
22.214.171.124.126.96.36.199 Olfactory receptors (ORs) are 7 TM
188.8.131.52.184.108.40.206.1 In the absence of ligand (odour), each
receptor has a characteristic basal activity.
Early guidance is activity-independent.
220.127.116.11.18.104.22.168 Neurons expressing the same OR
have similar cAMP signalling levels
(adenylate cyclase dependent;ACIII)
22.214.171.124.126.96.36.199.1 This determines the level of transcription
of familiar guidance cues (Robo/Slit,
188.8.131.52.184.108.40.206.1.1 This results in receptor/cue protein
levels characteristically associated
with expression of a particular OR,
which, in turn, determines mapping
in olfactory bulb (OB)
220.127.116.11.18.104.22.168.1.2 Disruption of guidance cue
expression (e.g. Neuropilin2)
disrupts regional mapping in OB
22.214.171.124.1.3 Conversion from
continuous to discrete map
126.96.36.199.1.3.1 Axons entering OB are
pre-sorted due to
188.8.131.52.184.108.40.206 Cue expression switches with time (e.g. from
Robo to Nrp/Sema) so that early entering axons
then guide later entering axons.
220.127.116.11.1.3.2 Sorting into glomeruli is
18.104.22.168.22.214.171.124 Activity drives higher cAMP levels which turns on
expression of homophilic adhesion molecules (Kirrels
and contactins), and Ephs and Ephrins (again!)
126.96.36.199.188.8.131.52.1 These interactions sort axons
expressing same ORs into groups
to form the glomeruli.
184.108.40.206.2 And, does this mean there is
also spatial organisation of
olfactory info in the cortex?
2.1 Choi et al. Cell (2011) vol. 146 (6) pp. 1004-15
2.1.1 Experimental strategy
220.127.116.11 Introduce ‘channelrhodospin’ (ChR2)
into subset of PC neurons
18.104.22.168.1 ChR2 is a light-activated cation
channel that stimulates action
potentials upon exposure to light
22.214.171.124.1.1 ie can ‘fire’ PC neurons
independent of mitral
126.96.36.199.2 Stimulate the ChR2+ subset of
neurons with light, paired with
either an aversive or appetitive
(appetite inducing) stimulus in
naïve (unconditioned) animals
(classic associative learning).
188.8.131.52.2.1 After conditioning, test whether light
stimulus alone can elicit the
appropriate behavioural response.
to PC neurons
184.108.40.206.3.1 3 ways (all using viruses)
220.127.116.11.3.1.1 Simplest: use
18.104.22.168.22.214.171.124 Hits 50% of cells
at injection site
126.96.36.199.3.1.2 Infect floxed* Chr2 into mouse in
which cre driven from Emx1
188.8.131.52.184.108.40.206 * These lox sites are in ‘flip’
orientation so cre will invert
the gene not delete it
220.127.116.11.18.104.22.168 Also hits 50%, but
22.214.171.124.3.1.3 Infect floxed* Chr2 at same
time as virus containing
synapsin driving cre
126.96.36.199.188.8.131.52 Much lower Chr2
2.1.2 ChR2 activation
184.108.40.206 Photostimulation (PS) of ChR2-expressing neurons
in the piriform cortex - the conditioned stimulus
(CS) - was paired with foot shock – the
unconditioned stimulus (US) - on only one side of
the chamber to condition the animals (10 pairings).
220.127.116.11.1 Animals then exhibited flight behaviour to
PS alone, but only when ChR2 was present
in piriform neurons (and a minimum of 200
had to be infected with ChR2).
18.104.22.168.2 Conditioning with odorants and PS together,
showed that subsequently either PS or
odorants could elicit flight.
2.1.3 ChR2 photostimulation can also
drive appetitive behaviours
22.214.171.124 Mice trained to take water in
response to odorant, could be
re-trained to respond instead
126.96.36.199 Male mice also could be trained to
associate presence of a female with either
an odour as the CS or with PS as the CS
2.1.4 Piriform cortex neurons are
plastic in their associative
188.8.131.52 The same set of
ChR2-expressing PC neurons
can be re-trained in either
184.108.40.206 Distinct sets of
ChR2-expressing PC neurons
can be trained and retrained
to elicit different behaviours
220.127.116.11 ie the piriform cortex is a
very plastic substrate
2.1.5 Does this prove that the
PC is the site of odorant
18.104.22.168 No, just shows that PC
can be used for
(What would prove it?)
22.214.171.124 However, does show that PC is very
plastic: apparently any group of ~200
neurons can be used to elicit diverse
behavioural associations, reversibly.
126.96.36.199.1 NB similar experiments in other regions of
the cortex (e.g. somatosensory) elicited a
specific behavioural output according to
location (ie topographically constrained).
Huber et al., 2008 Nature v451, p61
188.8.131.52 Nonetheless, strongly
suggests that random
connections from OB into
PC are used to associate
odours with particular
3 Responses to
3.1.1 Piriform cortex
184.108.40.206 Beyond the bulb…
220.127.116.11.1 As in the visual system, olfactory signals are relayed
from the bulb to multiple higher centres (e.g. SC,
LGN, then to cortex in visual system)
18.104.22.168.1.1 However, unlike the visual system, mitral cell
axons projecting to the piriform cortex (PC) do
not exhibit any spatial organisation
22.214.171.124.1.1.1 Correspondingly, individual odorants activate
subpopulations of neurons distributed across
126.96.36.199.188.8.131.52 NB Individual PC neurons respond to multiple, structurally dissimilar odorants
184.108.40.206 Is the piriform cortex the
site of olfactory learning?
220.127.116.11.1 Choi et al., (2011) test this using
optogenetic activation of arbitrary
subsets of PC neurons…..
3.1.2 How does the brain
odorant is which?
3.1.3 In mammals, the majority of
odors only drive behaviour after
learning. ie the significance of
odors is learnt by association.
18.104.22.168 However, it is not
known which brain
regions are involved.
3.2.1 Are all responses to odorants learned?
22.214.171.124 A small subset of odours elicit innate responses
126.96.36.199.1 e.g. trimethyl-thiazoline (TMT) from fox elicits fear (in mice!)
188.8.131.52.1.1 There are spatially invariant
projections from OB to cortical
amygdala that may be involved.
184.108.40.206.1.2 Similar bifurcation in flies……
3.2.2 Drosophila olfactory
system: conserved function