Reference number : GC-2017-Q1-02243, amendment number : , agreement type : G, recipient legal name : Molotchnikoff, Stéphane (Université de Montréal), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : During the last cycle my lab
investigated two themes. A) The influence of adaptation on changes of
preferred stimulus in visual cortex; our findings point to opportunities to explore plasticity of
neurons and neuronal networks. B) The functional
relationships between neurons forming a connectome. This topic suggests
a process of encoding neuronal signals. 
 Our research program aims to further develop
the above innovative topics in order to understand fundamental 
mechanisms of plasticity and the dynamics of population encoding in the CNS. Our proposed program deals with the two hottest
topics: plasticity and dynamics of connectomes. 
 Experiments are carried out on
anesthetized animals. Electrode matrices are lowered into the cortex. The
following specific subjects will be investigated. 
 A) Influence of an initial stimulus upon responses evoked
by a following stimulus. S timuli leave a trace. 
 In the initial phase we apply two types of stimuli. The first conditioning short stimulus is constant, that is,
exhibiting an identical property, the second conditioning
stimulus (same type) projects a variable property e.g.orientations. Conditioning stimuli are
followed at a predetermined interval by a test stimulus. The hypothesis is how each of the
conditioning stimuli affects the responses to the test stimulus? Does the peak of the orientation tuning curve shifts, i.e., do cells
change their selectivity? Do dynamic of cell's excitability change? The time course of this &ldquo;memory trace&rdquo; is examined. Responses are analyzed in term of rhythmicity and
synergy between recorded neurons. 
 B) Effects of serotonin/Fluoxetine
(S/F) and Ketamine . Adaptation shifts orientation tuning curve peaks, i.e., units acquire a new
selectivity. This adaptation-induced plasticity is facilitated
by S/F. Preliminary data show that ketamine opposes S/F effects. It is suggested that S/F
lower GABA levels, which increases plasticity in adult brains by enhancing BDNF
availability. We shall investigate the role of BDNF by blocking its
primary receptor: TrkB, with Cyclotraxine. Drugs are applied locally. 
 C) Adaptation in cortical layers . 
We showed that cells of the LGN resist adaptation. Layer 4 units (granular) are mostly driven by LGN. The question arises, how do cortical cells of layers 2,3, 5,6 change their
optimal orientation? Does adaptation-induced plasticity occur intrinsically within supra- and
infra-granular layers? This question leads
to our fourth goal. 
 D) Modulation of functional
relationships between neurons . The functional relationships between neurons
are revealed by the cross correlogram techniques. It discloses a connectome. The allegiance of
cells to a connectome changes depending upon stimulus. The 
working hypothesis is to determine if in addition to classical neuronal selectivity, there is a correlating change in connectome
selectivity signaling. In addition how connectome in area 17 is read in area 18?, program purpose french : During the last cycle my lab
investigated two themes. A) The influence of adaptation on changes of
preferred stimulus in visual cortex; our findings point to opportunities to explore plasticity of
neurons and neuronal networks. B) The functional
relationships between neurons forming a connectome. This topic suggests
a process of encoding neuronal signals. 
 Our research program aims to further develop
the above innovative topics in order to understand fundamental 
mechanisms of plasticity and the dynamics of population encoding in the CNS. Our proposed program deals with the two hottest
topics: plasticity and dynamics of connectomes. 
 Experiments are carried out on
anesthetized animals. Electrode matrices are lowered into the cortex. The
following specific subjects will be investigated. 
 A) Influence of an initial stimulus upon responses evoked
by a following stimulus. S timuli leave a trace. 
 In the initial phase we apply two types of stimuli. The first conditioning short stimulus is constant, that is,
exhibiting an identical property, the second conditioning
stimulus (same type) projects a variable property e.g.orientations. Conditioning stimuli are
followed at a predetermined interval by a test stimulus. The hypothesis is how each of the
conditioning stimuli affects the responses to the test stimulus? Does the peak of the orientation tuning curve shifts, i.e., do cells
change their selectivity? Do dynamic of cell's excitability change? The time course of this &ldquo;memory trace&rdquo; is examined. Responses are analyzed in term of rhythmicity and
synergy between recorded neurons. 
 B) Effects of serotonin/Fluoxetine
(S/F) and Ketamine . Adaptation shifts orientation tuning curve peaks, i.e., units acquire a new
selectivity. This adaptation-induced plasticity is facilitated
by S/F. Preliminary data show that ketamine opposes S/F effects. It is suggested that S/F
lower GABA levels, which increases plasticity in adult brains by enhancing BDNF
availability. We shall investigate the role of BDNF by blocking its
primary receptor: TrkB, with Cyclotraxine. Drugs are applied locally. 
 C) Adaptation in cortical layers . 
We showed that cells of the LGN resist adaptation. Layer 4 units (granular) are mostly driven by LGN. The question arises, how do cortical cells of layers 2,3, 5,6 change their
optimal orientation? Does adaptation-induced plasticity occur intrinsically within supra- and
infra-granular layers? This question leads
to our fourth goal. 
 D) Modulation of functional
relationships between neurons . The functional relationships between neurons
are revealed by the cross correlogram techniques. It discloses a connectome. The allegiance of
cells to a connectome changes depending upon stimulus. The 
working hypothesis is to determine if in addition to classical neuronal selectivity, there is a correlating change in connectome
selectivity signaling. In addition how connectome in area 17 is read in area 18?, agreement title english : Etudes des mécanismes de l'adaptation et des relations interneuronales au cortex., agreement title french : Etudes des mécanismes de l'adaptation et des relations interneuronales au cortex., agreement number : RGPIN, agreement value : 125000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada