PhD J. Tiago Goncalves

Our lab studies the circuit physiology of the hippocampus, and specifically how environment, aging and inflammation can modulate memory and learning. We use state-of-the-art in vivo two-photon Ca²⁺ imaging techniques in awake mice and we were pioneers in applying these imaging methodologies to the study of adult neurogenesis in the dentate gyrus (DG) of the hippocampus (Gonçalves et al. 2016a). 

The DG is one of the few regions of the mammalian brain that keeps adding new neurons through adulthood in what probably constitutes the most robust form of neuronal plasticity in the adult brain. Adult-born neurons contribute to memory formation and defects in neurogenesis have been associated with several human neurological and psychiatric diseases such as epilepsy, Alzheimer’s and schizophrenia. In addition adult-born neurons have also been used to study neuronal development.

We are particularly interested in understanding how adult neurogenesis in the DG may support hippocampal function, playing a role in memory and learning. In order to understand the function of adult-born neurons in the circuits underlying spatial memory we are studying the encoding of position in the hippocampus, including ‘place cells’ i.e. neurons that fire primarily when an animal is at a specific location.

Hemos descubierto anteriormente que la neurogénesis adulta mejora la precisión de las representaciones neuronales del espacio en ratones jóvenes (Frechou et al. 2022), cuando los ratones se colocan en un contexto nuevo. También descubrimos que estas representaciones, que codifican la posición del ratón dentro de su entorno, se vuelven menos precisas a medida que los animales envejecen (McDermott et al. 2023). Nuestro trabajo actual se basa en estos hallazgos iniciales para identificar las vías moleculares y celulares que median los efectos del entorno en la memoria espacial y la cognición.

Direcciones actuales

Actualmente estamos investigando el papel de la microglia y las vías neuroinmunes en la formación de recuerdos y representaciones neuronales del espacio en el hipocampo. Además, estamos interesados en identificar los determinantes moleculares de la codificación espacial mediante la obtención de perfiles transcripcionales de neuronas previamente obtenidas por imágenes, estableciendo así un vínculo entre las propiedades de codificación molecular y neuronal de las células individuales.

Frechou M.A., Martin S.S., McDermott K.D., Huaman E.A., Gokhan S., Tomé W.A., Coen-Cagli R., Gonçalves J.T., Adult neurogenesis improves spatial information encoding in the dentate gyrus, Nat Commun., 15(1):6410 (2024)

McDermott K.D., Frechou M.A., Martin S.S., Jordan J.T., Gonçalves J.T., Delayed formation of neural representations of space in aged mice, Aging Cell, e13924 (2023)

Jordan J.T., McDermott K.D., Frechou M.A., Shtrahman M.,Gonçalves J. T., Treadmill-based task for assessing spatial memory in head-fixed mice, STAR Protoc., 2, 100770 (2021) 

Guo N., McDermott K.D., Shih Y.T., Zanga H., Ghosh D., Gonçalves J.T., Sahay A., Transcriptional regulation of neural stem cell expansion in the adult hippocampus, eLife, 11:e72195 (2022) PMCID: PMC8820733

Nasrallah K., Frechou M.A., Yoon Y.J., Persaud S., Gonçalves J.T., Castillo P.E., Seizure-induced strengthening of a recurrent excitatory circuit in the dentate gyrus is proconvulsant, PNAS 119(32):e2201151119 (2022)

Gronska-Peski M., Gonçalves J.T., Hébert J.M., Enriched Environment Promotes Adult Hippocampal Neurogenesis through FGFRs. J. Neurosci.;41(13), 2899-2910 (2021) 

Mansour A.A., Gonçalves J.T., Bloyd C., Li H., Fernandes S., Quang D., Johnston S., Parylak S., Jin X., Gage F.H., An in vivo model of functional and vascularized human brain organoids, Nature Biotech., 36(5), 432-441 (2018)

Gonçalves J. T. *, Schafer S.T. * (equal contribution), Gage F.H., Adult neurogenesis in the hippocampus: from stem cells to behavior, Cell, 167, 897-914 (2016)

Gonçalves J.T., Bloyd C.W., Shtrahman M, Johnston S.T., Schafer S.T., Parylak S.L., Thanh T., Chang T., Gage F.H., In vivo imaging of dendritic pruning in dentate granule cells, Nat. Neurosci., 19(6), 788-791 (2016)