Innovating Works

PGC2018-095980-B-I00

Financiado
DE ATRAS HACIA DELANTE: PARTICIPACION DE LA VIA CEREBELO-CORTEZA INFRALIMBICA EN...
DE ATRAS HACIA DELANTE: PARTICIPACION DE LA VIA CEREBELO-CORTEZA INFRALIMBICA EN LA FORMACION DE HABITOS DE INCENTIVO INDUCIDA POR DROGAS ADICTIVAS ADDICTION IS A CHRONIC BRAIN DISORDER CHARACTERISED BY COMPULSIVE DRUG CONSUMPTION AND HIGH RISK OF RELAPSE, IT HAS BEEN HYPOTHESISED THAT COMPULSIVE BEHAVIOUR MAY RESULT FROM AN ABERRANT HABIT FORMATION, IN FACT, PATIENTS SUFFERI... ADDICTION IS A CHRONIC BRAIN DISORDER CHARACTERISED BY COMPULSIVE DRUG CONSUMPTION AND HIGH RISK OF RELAPSE, IT HAS BEEN HYPOTHESISED THAT COMPULSIVE BEHAVIOUR MAY RESULT FROM AN ABERRANT HABIT FORMATION, IN FACT, PATIENTS SUFFERING FROM COMPULSIVE DISORDERS INCLUDING OCD, DRUG ADDICTION, AND TOURETTE SYNDROME HAVE DEMONSTRATED TO DEVELOP HABITS MORE EASILY THAN NORMAL CONTROLS, AFTER REDUCED BEHAVIOURAL TRAINING, INTERESTINGLY, THE MAJORITY OF THE STUDIES ABOUT COMPULSIVE DISORDERS HAVE SHOWN SMALLER CEREBELLAR SIZE AND REDUCED ACTIVITY IN RESTING STATE, HABITS CONSIST IN OVERLEARNED, REPETITIVE, SEQUENTIAL BEHAVIOURS THAT ARE PERFORMED AUTOMATICALLY AND TRIGGERED BY ASSOCIATED ENVIRONMENTAL SIGNALS, DURING ACQUISITION OF HABITS, THERE IS A SHIFT FROM GOAL-DIRECTED BEHAVIOUR REGULATED BY AN ACTION-OUTCOME PROCESS (RESPONSE-OUTCOME; R-O) TO AUTOMATIZED BEHAVIOUR TRIGGERED BY THE ASSOCIATED STIMULUS (STIMULUS-RESPONSE; S-R), REMARKABLY, BOTH REPRESENTATIONS (R-O AND S-R) SURVIVE IN PARALLEL AND PREDOMINATE OVER EACH OTHER DEPENDING ON INTERNAL AND EXTERNAL CONDITIONS, WITH EXTENDED DRUG EXPERIENCE, THE BALANCE BETWEEN FLEXIBLE (R-O) AND AUTOMATIC (S-R) BEHAVIOURAL PATTERNS CAN BE BIASED TOWARDS HABITS, THE INFRALIMBIC CORTEX (IL) HAS DEMONSTRATED TO BE A KEY REGION IN THE FORMATION OF HABITS, REPEATED OPTOGENETIC INHIBITION OF THE IL DURING OVERTRAINING DISRUPTS HABIT FORMATION, THE CEREBELLUM ALSO PARTICIPATES IN THE ESTABLISHMENT OF HABITS, IT HAS BEEN DESCRIBED THAT REGIONALISED CEREBELLAR LESIONS PREVENT THE DEVELOPMENT OF HABITS, VERY RECENT FINDINGS FORM OUR LABORATORY INDICATE THAT THE CEREBELLUM CAN CONTROL COCAINE-DEPENDENT ACTIVITY AND PLASTICITY IN THE IL, A LESION OF THE CEREBELLUM INCREASED ACTIVITY AND PERINEURONAL EXPRESSION IN THE IL, IN SEARCHING FOR A NEUROANATOMICAL MODEL TO EXPLAIN THESE RESULTS, A TRACING STUDY USING ANTEROGRADE AND RETROGRADE TRACERS REVEALED A DIRECT PATHWAY FROM THE LATERAL CEREBELLAR NUCLEUS TO THE CONTRALATERAL VTA, THEREFORE, THE MAIN GOAL OF THE PRESENT PROPOSAL IS TO INVESTIGATE THE CONTRIBUTION OF THE CEREBELLUM-INFRALIMBIC PATHWAY TO THE DEVELOPMENT OF DRUG-INDUCED HABITS USING INNOVATIVE METHODOLOGIES SUCH AS DREADDS (DESIGNER RECEPTOR EXCLUSIVELY ACTIVATED BY DESIGNER DRUG), ELECTROPHYSIOLOGY AND OPTOGENETICS, THIS PROJECT WILL HAVE 3 INTERCONNECTED AND COMPLEMENTARY AIMS THAT WILL ANSWER THE FOLLOWING 3 MAIN QUESTIONS: 1) AIM 1, DOES THE STIMULATION OF THE CEREBELLAR CORTEX REDUCE THE HABIT BIAS THAT DRUGS INDUCE IN NATURAL-REWARDED BEHAVIOUR? 2) AIM 2, DOES THE CEREBELLUM MODULATE THE FUNCTION OF IL IN DRUG-INDUCED HABIT FORMATION? 3) AIM 3, IS THE CEREBELLAR CONTRIBUTION TO HABIT FORMATION MEDIATED THROUGH THE VTA AND DOPAMINERGIC ACTIVITY? TAKEN TOGETHER, THE OBJECTIVES OF THE PRESENT PROPOSAL AIM TO TEST THE HYPOTHESIS THAT BY MODULATING ACTIVITY IN THE CEREBELLUM IS POSSIBLE TO CHANGE THE BALANCE BETWEEN FLEXIBLE GOAL-DIRECTED AND HABITUAL BEHAVIOURAL PATTERNS, IN ADDITION, WE HYPOTHESISE THAT RESTORING NORMAL ACTIVITY IN THE CEREBELLUM-IL PATHWAY WOULD RESULT IN THE REDUCED PROPENSITY TO EXHIBIT DRUG-RELATED BEHAVIOUR INSENSITIVE TO DEVALUATION, THIS PROPOSAL HAS BEEN DESIGNED IN COLLABORATION WITH ONE OF THE MOST IMPORTANT INSTITUTIONS IN NEUROSCIENCE IN THE WORLD, THE ALBERT EINSTEIN COLLEGE OF MEDICINE, CEREBELO\INFRALIMBICO\AREA TEGMENTO VENTRAL\ALCOHOL\COCAINA\DREADDS\OPTOGENÉTICA\ELECTROFISIOLOGÍA ver más
01/01/2018
FUEUJI
85K€
Perfil tecnológico estimado

Línea de financiación: concedida

El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2018-01-01
Presupuesto El presupuesto total del proyecto asciende a 85K€
Líder del proyecto
UNIVERSITAT JAUME I DE CASTELLÓ No se ha especificado una descripción o un objeto social para esta compañía.
Total investigadores 2