Uconn Abroad ProgramJune 2014
Long term auditory lesion plasticity :On how the nervous system responds to
the auditory cortex ablation.
1899 –Term plasticity
INDEX
1. KEY CONCEPTS IN NEUROPLASTICITY.2. ASCENDING-DESCENDING FEEDBACK LOOPS IN THE
AUDITORY PATHWAY.3. AN ANIMAL MODEL OF RESTRICTED CORTICAL ABLATION
FOR EXPLORING THE ROLE OF THE DESCENDING CONNECTIONS AND PLASTIC REPAIR OF THE CENTRAL AUDITORY PATHWAY.
4. PAPERS I – FEEDBACK LOOP N3 – CORTICO-COLLICULAR CONNECTIONS. (C-FOS,CALRETININ AND MASSIVE GENE ANALYSIS OF THE MIDBRAIN)
5. PAPERS II – FEEDBACK LOOP N4 – CORTICO PONTINE CONNECTIONS. (ABRS AND Q-PCR ANALYSIS OF THE INNER EAR.
“nerve cell processes have amoeboid movement and contacts
between terminal axonal branches and the soma and dendrites could
loosen by protoplasmic retraction. In this way, dissociation would
take place with the consequent functional rest of the cells. Thus
during sleep, dendrites of pyramidal cells would shrink and cease
excitation arriving from the sense organs” (p. 189, Cajal, 1899)
Santiago Ramón y Cajal
A review that I recommend to read…Cajal and brain plasticity: Insights relevant to emerging concepts of mind.Efrain C. Azmitia�Center for Neural Science, NewYork University,, USABrain Res. Rew. 55 (2007) 395-405
Learning and memorySynaptic plasticity: Homesotatic / HebbianLesionalDevelopmental / AdultOthers – Functional, cross-modal, ultrastructural, topographic and dynamic representational, residual, anatomical, etc.
CURRENTLY NEURAL PLASTICITY IS A WIDE CONCEPT WITH MANY DIFFERENT MEANINGS
HOWEVER FOR SOME GROUPS OF NEUROSCIENTIST, PLASTICITY IS SIMPLY HOW THE BRAIN WORKS !!!
Neuroplasticity = Brain function
•What kind of changes can trigger neuronal plasticity programs?❧External induction. Environmental interaction❧Internal activation. Immunological or Genomic changes
•What are the basic tools ?•Anatomical -❦Changes in number of functional units (Neurons) of the networks. (Apoptosis and cell proliferation).❦Rewiring – Collateral sprouting and pruning.•Functional -❦Adjustment of synaptic strength ❦Changes in genomic and protein synthesis
What are the fundamentals of neuroplasticity?Plasticity is basically networks reorganization
1899 –Term plasticity
INDEX
1. KEY CONCEPTS IN EUROPLASTICITY.2. ASCENDING-DESCENDING FEEDBACK LOOPS IN THE
AUDITORY PATHWAY.3. AN ANIMAL MODEL OF RESTRICTED CORTICAL ABLATION
FOR EXPLORING THE ROLE OF THE DESCENDING CONNECTIONS AND PLASTIC REPAIR OF THE CENTRAL AUDITORY PATHWAY.
4. PAPERS I – FEEDBACK LOOP N3 – CORTICO-COLLICULAR CONNECTIONS. (C-FOS,CALRETININ AND MASSIVE GENE ANALYSIS OF THE MIDBRAIN)
5. PAPERS II – FEEDBACK LOOP N4 – CORTICO PONTINE CONNECTIONS. (ABRS AND Q-PCR ANALYSIS OF THE INNER EAR.
The Auditory PathwayAscending inputs to the auditory cortex originate a descending top down control that is able to change the
way of processing of all relay stations of the pathway, from the inner ear to the thalamus
The AP is functionally organized in feedback loops
1899 –Term plasticityINDEX
1. KEY CONCEPTS IN EUROPLASTICITY.2. ASCENDING-DESCENDING FEEDBACK LOOPS IN THE
AUDITORY PATHWAY.3. AN ANIMAL MODEL OF RESTRICTED CORTICAL ABLATION
FOR EXPLORING THE ROLE OF THE DESCENDING CONNECTIONS AND PLASTIC REPAIR OF THE CENTRAL AUDITORY PATHWAY.
4. PAPERS I – FEEDBACK LOOP N3 – CORTICO-COLLICULAR CONNECTIONS. (C-FOS,CALRETININ AND MASSIVE GENE ANALYSIS OF THE MIDBRAIN)
5. PAPERS II – FEEDBACK LOOP N4 – CORTICO PONTINE CONNECTIONS. (ABRS AND Q-PCR ANALYSIS OF THE INNER EAR.
Which anatomical, functional and metabolicreorganization take place in the AP after theloss of the corticofugal projection?
Are they these changes reversible?
t
1899 –Term plasticity
INDEX
1. KEY CONCEPTS IN EUROPLASTICITY.2. ASCENDING-DESCENDING FEEDBACK LOOPS IN THE
AUDITORY PATHWAY.3. AN ANIMAL MODEL OF RESTRICTED CORTICAL ABLATION
FOR EXPLORING THE ROLE OF THE DESCENDING CONNECTIONS AND PLASTIC REPAIR OF THE CENTRAL AUDITORY PATHWAY.
4. FEEDBACK LOOP N3 – CORTICO-COLLICULAR CONNECTIONS. (C-FOS,CALRETININ AND MASSIVE GENE ANALYSIS OF THE MIDBRAIN). COCLEOTOPY (C Fos)
5. FEEDBACK LOOP N4 – CORTICO PONTINE CONNECTIONS. (ABRS AND Q-PCR ANALYSIS OF THE INNER EAR.
3How to respond tosound the IC when partof the descendingprojection is lost?
Nervous system self-repairs ?
Three parameters were measured to analyze the fosactivation by sound in groups of normal and lesionedrats :
Total number of neurons
Density of the immunoreaction
Perimeter
c - Fos immunoractivity analysis :1. Sterology2. Topographic densitometry maps. Positional
values of each particle segmented in 2D (0-88) and gray level were fed into MATLAB.
3. Morphometry. The perimeter of all nuclei c-Fos Ir (0-88) in all experimental case wasmeasured with Image J.
Low
High
3 Perimeter2 Gray Values
1 Total number of ir-neurons
Fos activation
Neuronal nucleus
Chromogen
Many IC neurons lose their sensitivity tosound after removing the AC. However are recovered in the long term.
These changes are only functional orstructural?.In other words the decrease and recoveryin fos-ir activation is due to a transientdrop in function by the lost of connection(residual plasticity) or to an active plasticmechanism ?
Activity-dependent changes- Ca++ and Calretinin Homeostasis of Ca2+
Synaptic plasticity depend from changes in intracellular Ca2+ (2ndmessengers).
CR Ca2+ Binding proteide - EF-hand protein familiy
FUNCTION
MODULATOR OFNEURONAL DISCHARGE
Fast and slow Ca2 + Buffer
Fast trasporter of Ca2+Ca2+ modulation of receptor synthesis
1899 –Term plasticity
INDEX
1. SOME GENERAL IDEAS ABOUT PLASTICITY.2. ASCENDING-DESCENDING FEEDBACK LOOPS IN THE
AUDITORY PATHWAY.3. AN ANIMAL MODEL OF RESTRICTED CORTICAL ABLATION
FOR EXPLORING THE ROLE OF THE DESCENDING CONNECTIONS AND PLASTIC REPAIR OF THE CENTRAL AUDITORY PATHWAY.
4. PAPERS I – FEEDBACK LOOP N3 – CORTICO-COLLICULAR CONNECTIONS. (C-FOS,CALRETININ AND MASSIVE GENE ANALYSIS OF THE MIDBRAIN)
5. PAPERS II – FEEDBACK LOOP N4 – CORTICO PONTINE CONNECTIONS. (ABRS AND Q-PCR ANALYSIS OF THE INNER EAR.
Modified from John J. Guinan, Jr.
AuditoryCortex
MOC = OHCB (Outher hair cell bundle)LOC = IHCB (Inner hair cell bundle)
Efferent pathway
Mainly ContralateralMainly Ipsilateral
Which is the effect?
Modified from John J. Guinan, Jr.
Auditory Cortex
MOC = OHCB (Outher hair cell bundle)LOC = IHCB (Inner hair cell bundle)
Modified from John J. Guinan, Jr.
Auditory Cortex
MOC = OHCB (Outher hair cell bundle)LOC = IHCB (Inner hair cell bundle)
Lost of excitation on LOC and MOCDecrease in SOC activityIncrease in CAP and ABRS ?????Decrease in CM ?????
A tube length of 24 cm resulted in an air conduction time of 0.75 ms forthe stimulus to arrive at the tympanic membrane.Stimuli -> 0.1 ms alternating polarity click with a repetition rate of 11bursts/s. delivered in 10 dB ascending steps from 30 to 90 dB (SP). Thisdelay was added to the 1 ms prestimuli period to calculate the onset ofthe ABR (1.7 ms). Responses were averaged 1000 times
SUMMARY OF THE MAIN FINDINGS
1 DAY PL 7 DAYs PL 15 DAYs PL 30 DAYs PLControlTreshold and amplitudes
So it's no problem. The effect of AC lesions on the IC was primarily direct.
However … What happens when we analyzed the latencies of ABRS waves?
We hypothesize that shorter waves latencies at long term can be due to alterations in gaincontrol and cochlear amplification. Broad frequencies responses need less time to be elaboratedand consequently produces faster responses from the cochlea.
NEXT STATION - TERMINAL :
EFFERENT SYSTEM AND PRESTIN
glud1
GluA2
GluA3
GluA4
Pvα
α7 Ach
α10 Ach
D1
D2
α1 GABA
γ2 GABA
Prestin
LOC
MOC
Glutamate
Neu
riotrasmisssio
nGAB
Areceptors
IHC OHC
LOCCholinergic
LOCDopaminergic
Unmyelinated
Myelinated
MOC
Type I
Type II
α9/α10 nAch
AMPA GluRs
D1 Rs
D2 Rs
Maison et al., J Neurosci. 2012.
EXPERIMENTAL GROUPS – SINGLE RESTRICTED AUDITORY CORTEX ABLATION1, 7 AND 15 DAYS AFTER SURGERY.
IHC Ca reg.
Activation of nicotinic α9α10 acetylcholine receptors results in the inward Ca2+ current that activates nearby Ca2+-dependent K+ channels. This effect is amplified by Ca2+-induced
Ca2+-release from synaptoplasmic cistern.
Frolenkov G I J Physiol 2006;576:43-48
©2006 by The Physiological Society
MOC OHC ContraLOC IHC Ipsi
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