Olfactory Circuits: From Development to Function. Laboratory for Perception and Memory. Institut Pasteur & CNRS. Page 2. L'autopoïèse du système olfactif ...
• Immunohistochemistry in fixed OB slices shows that OMP labelling is unchanged by MAM treatment, but gap43 labelling is significantly reduced
Release Probability I: Paired-Pulse Responses
100 μV
A
B
Release Probability II: MK-801 Experiments
Summary - Part 1
• Reducing the number of immmature sensory neuron inputs to the OB, reduces the overall release probability, but no change in AMPA:NMDA ratio, or quantal size in the projection. • So, the physiological properties of newborn OSNs are quite different from their more mature counterparts.
Three Main Objectives
(1) Neurogenesis of sensory neurons
(2) Neurogenesis in the central relay
?
(3) Functional significances
Part II. Bulbar Neurogenesis
Perinatal Neurogenesis
Identifying Newborn Neurons in Adult Olfactory Bulb
Olfactory Bulb
Adult-born neuron
20 μm
Trends in Neurosciences 28, 248-254 (2005).
Becoming a neuron from a glia cell EPL MCL GCL
RMS
Nat. Neurosci. 6, 507-518 (2003).
Early versus Late Neurogenesis
Adult
Summary - Part 2
• Adult Neurogenesis Does Not Recapitulate Embryogenesis. Embryogenesis • It Offers a Unique Situation in which Epigenetic Regulations May Take Place.
Activity-depend regulation
Maturation of GABAergic Interneurons Lentivirus-GFP
Cortex
Accessory OB
SVZ LV
Main OB RMS
Neuron 46, 103-116 (2005)
Spine Density of Newborn Neurons
Open
Closed
Neuron 46, 103-116 (2005)
Spine Density of Mature Neurons Open Open
Closed Closed
Neuron 46, 103-116 (2005)
Summary - Part 3
• Adult Neurogenesis Offers a Unique Situation in which Activity-Dependent Regulations May Take Place. Place
Three Main Objectives
(1) Neurogenesis of sensory neurons
(2) Neurogenesis in the central relay
?
(3) Functional significances
Olfactory Discrimination Learning ? MOR23-GFP
?
S+
S-
S+/S-
S+/-
S+
J. Neurosci. 26, 10508-13 (2006)
Computational Functions
Three Glutamatergic Inputs
TB Stimulations at Excitatory Synapses
Newborn Interneurons Display LTP A
B
3-week-old GC
Nat. Neurosci. 12, 728-730 (2009).
Synaptic plasticity
Computational functions
EPSC amplitude (%)
TBS 250 newborn mature
200
150
100
50
-5
0
5
10 Time (min)
15
20
25
Newborn Interneurons are Transiently Amenable
4
6
When time matters A
B 600
BrdU
BrdU+ cell density
Perfusion
Learning
500
400
300
200
100 0
5
15
25
35
45
55
65
0
11
18
23
30
38
65
Days
Days BrdU
D T1
T2
T3
T4
T5
T6
50 Linalol 10-2
10-3
10-4
10-5
10-6
**
**
130
T7
100
10-2
**
Norm. BrdU+ cell density
Correct responses (%)
C
10-7
0
** 110
90
70 C
T
C
T
C
T
C T
C
T
C
T
50 1
5
10 1
5
10 1
5
10 1
5
Blocks
10 1
5
10 1
5
10 1
5
10
11
18
23
30
38
65
Days J. Neurosci. 28: 11511-6 (2009)
Deciphering the Function of New Neurons
Newborn Interneurons Labeled with YFP
Action Potential Evoked by Flash of Blue Light
REC Blue Light
Light-Induced Excitability of Newborn Interneurons
Remote Control of Adult-born Neurons to Inhibit Output Neurons a
Rec.
Light
Adult-born neurons
d
Neuronal target
e
f Light evoked GABAergic currents: n = 32
GZ block: n = 7 / 7 cells
Origin and Location of the Synaptic Contacts from Newborn Neurons
Mechanisms of Light-induced GABA Release
Post-synaptic target
Adult-born neuron
Mature GABAergic interneurons and Synchronization A
B
B
C
10 mV
250 ms
J. Neurosci. 19, 10727 (1999)
Oscillations Depends on Inhibition
Reducing Neurogenesis Decreases oscillations
Ctrl
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Reducing Neurogenesis Increases Reaction Time
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Ctrl Irrad. Irrad.
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Newborn neurons for discrimination
Conclusions 1) New neurons form an integral part of the normal function circuitry. 2) This process is not fixed, and does not recapitulate embryogenesis, it’s much more…
Conclusion
Adult neurogenesis is a form of metaplasticity: a change in the brain facilitating further changes in the brain.
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