Investigador responsable del grupo: Zafar U. Khan
Área temática: Neurociencia
Memory defines our identity and is not only essential for daily life activities but also fundamental for shaping our future. Long-lasting memories are therefore critical for survival. Memory formation occurs in two phases: a labile short-term phase lasting from minutes to hours, and a stable long-term phase that can persist from days to a lifetime. Labile memory is temporarily maintained through increased intrinsic neuronal excitability, remains highly vulnerable to interference, and rapidly decays if not stabilized. The consolidation of newly acquired labile memories involves several temporally distinct stages: encoding, synaptic consolidation, and systems consolidation. Encoding occurs within seconds, whereas synaptic consolidation unfolds over hours and is characterized by structural plasticity and the stabilization of synaptic connectivity within local neural circuits. Systems consolidation, in contrast, requires a prolonged reorganization of memory representations across distributed brain networks. The transition from labile memory to an early-phase stable memory represents a critical stabilization step that prevents memory loss and initiates the transformation of newly encoded experiences into long-lasting memories. Disruptions in this conversion process are likely to contribute to the memory deficits associated with aging, Alzheimer’s disease, and other neurological disorders. While extensive research has focused on encoding and later stages of synaptic consolidation, the mechanisms that convert labile memory into an early-phase stable form remain largely unexplored, and the temporal boundaries of this early stabilization phase are poorly defined in current models of memory consolidation. Our laboratory aims to fill this fundamental gap in memory research by uncovering the cellular and molecular mechanisms that stabilize labile memory and by determining how disruptions in this process lead to memory impairments.
Contacto
Laboratorio de Neurobiología, 2a Planta
Centro de Investigaciones Médico Sanitaria (CIMES)
Universidad de Málaga, Campus Teatinos
C/ Marqués de Beccaria, 3, 29010 Málaga, Spain
Correo electrónico: memorylabmalaga@uma.es
ZAFAR U. KHAN
Profesor Contratado Doctor. Departamento de Medicina y Dermatología. Universidad de Málaga
Teléfono: 952 13 72 79
Correo electrónico: zkhan@uma.es
Biography
Dr. Zafar is a neuroscientist with more than 35 years of research experience. He received his Ph.D. in Biochemistry from the University of Delhi, where his work contributed to the discovery of lipid transfer proteins involved in intracellular phospholipid transport. He subsequently conducted postdoctoral research at the University of Kansas Medical Center, where he identified two new forms of phospholipid transport proteins in the brain. He later joined the University of Missouri–Kansas City, where his research focused on the characterization and functional organization of pentameric GABAA receptors. In 1996, Dr. Zafar was appointed Scientist at the Yale University School of Medicine, where he served as Principal Investigator of the Neurochemistry Laboratory. At Yale, he investigated the molecular mechanisms underlying schizophrenia. His research demonstrated for the first time that dopamine D2 receptors in astroglial cells play a crucial role in calcium regulation and contribute to working memory deficits associated with schizophrenia. This work highlighted the importance of glial cells in cognitive function and provided new insights into the cellular mechanisms of schizophrenia. Since joining the University of Málaga in 2002, Dr. Zafar has established the Neurobiology Laboratory at CIMES and MemoryLab Málaga at IBIMA, establishing a leading hub for research on memory and neural function. He also founded the PAIDI-CTS 586 research group of the Junta de Andalucía, which brings together 35 researchers, including international collaborators, to advance neuroscience in the region. Under his leadership, his team has published extensively in high-impact journals, registered several patents, and launched a biotechnology spin-off company recognized with the first prize from the Chamber of Commerce of Málaga. His current research focuses on the cellular and molecular mechanisms that underlie memory stabilization and how disruptions in these processes contribute to memory deficits in aging, Alzheimer’s disease, and schizophrenia.
- Neurobiology of Memory Processing – Investigating the cellular and molecular mechanisms underlying the encoding, stabilization, and retrieval of memory.
- Structural Plasticity and Memory Enhancement – Studying how changes in synaptic and neuronal structure contribute to memory formation and cognitive improvement.
- Prevention and Reversal of Memory Deficits – Exploring strategies to prevent or reverse memory impairments associated with aging, Alzheimer’s disease, schizophrenia, and other neurological disorders.
Imagine waking up one morning and not recalling who you are, who is sitting next to you, or what you did yesterday. Memory is essential for our sense of identity and survival. Intact memory allows us to carry out daily life activities, such as managing finances, taking medications on time, navigating unfamiliar environments, remembering a grandchild’s birthday, or learning to use a new computer.
Our laboratory aims to understand how newly acquired, labile memories are transformed into stable, long-lasting memories, and what goes awry in these processes that leads to memory loss. Currently, our research focuses on the following objectives:
- Cellular and molecular mechanisms of memory stabilization – elucidate how newly acquired memories become long-lasting.
- Synaptic and structural plasticity in cognition – define how neuronal remodeling supports memory consolidation and enhancement.
- Mechanisms of memory deficits – determine how disruptions in memory stabilization contribute to cognitive decline in aging, Alzheimer’s disease, and schizophrenia.
CTS-586, Junta de Andalucía
Estudio de los procesos biológicos asociados a trastornos mentales y enfermedades neurológicas
CB06/05/1116, CIBERNED, Instituto de Salud Carlos III
Enfermedad de Alzheimer y otras demencias neurodegenerativas
CTS-586-G-FEDER, Fondo Europeo de Desarrollo Regional
Recuperation of cognitive functions in schizophrenia
PROYEXCEL-00422, Junta de Andalucía
Biological underpinnings of the transformation of a labile memory into a long lasting long-term memory
PID2022-136954OB-I00, Agencia Estatal de Investigación, Ministerio de Ciencia, Innovación y Universidades
Molecular mechanisms of conversion of a labile memory into a long-lasting memory and their relevance to memory deficits in aging and Alzheimer´s disease
Group members
Zafaruddin Khan
Elisa Martin Montañez
Elena Vila Herrero
Irene Navarro Lobato
Sinforiano José Posadas Mañanes
Cristina Anable Muñoz de León López
Alicia Prieto Cañamero
Collaborators
Antonia Vlahou, Biomedical Research Foundation, Academy of Athens, Greece
Lisa Genzel, Donders Centre for Neuroscience, Radboud University, Netherlands
Zafar Bashir, University of Bristol, United Kingdom
David Fernández de Sevilla, Universidad Autónoma de Madrid, Spain
Imran Ahmad, Jina Pharmaceuticals Inc., Chicago, USA
López-Aranda MF, López-Téllez JF, Navarro-Lobato I, Masmudi-Martín M, Gutierrez A, Khan ZU (2009) Role of layer 6 of V2 visual cortex in object recognition memory. Science 325: 87-89. doi: 10.1126/science.1170869.
López-Téllez JF, López-Aranda MF, Navarro-Lobato I, Masmudi-Martín M, Martín-Montañez E, Blanco E, Khan ZU (2010) Prefrontal inositol tri-phospate is molecular correlate of working memory in non-human primates. Journal of Neuroscience30(8): 3067–3071. doi: 10.1523/JNEUROSCI.4565-09.2010.
Masmudi-Martín M, Navarro-Lobato I, López-Aranda MF, Delgado G, Martín-Montañez E, Quiros-Ortega ME, Carretero-Rey M, Narváez L, Garcia-Garrido MF, Posadas S, López-Téllez JF, Blanco E, Jiménez-Recuerda I, Granados-Durán P, Paez-Rueda J, López JC, Khan ZU (2019) RGS14 414 treatment induces memory enhancement and rescues episodic memory deficits. FASEB Journal 33(11): 11804-11820. doi: 10.1096/fj.201900429RR.
Navarro-Lobato I, Masmudi-Martín M, López-Aranda MF, Quiros-Ortega ME, Carretero-Rey M, Garcia-Garrido MF, Gallardo-Martínez C, Martín-Montañez E, Gaona-Romero C, Delgado G, Torres-Garcia L, Terrón-Melguizo J, Posadas S, Muñoz LR, Rios CV, Zoidakis J, Vlahou A, López JC, Khan ZU (2022)RGS14414-mediated activation of the 14-3-3ζ in rodent perirhinal cortex induces dendritic arborization, an increase in spine number, long-lasting memory enhancement, and the prevention of memory deficits. Cereb Cortex 32(9):1894-1910. doi: 10.1093/cercor/bhab322.
Camacho-Conde JA, Del Rosario Gonzalez-Bermudez M, Carretero-Rey M, Khan ZU (2023) Therapeutic potential of brain stimulation techniques in the treatment of mental, psychiatric, and cognitive disorders.CNS Neuroscience & Therapeutics 29(1):8-23. doi: 10.1111/cns.13971.
Navarro Lobato I, Aleman-Zapata A, Samanta A, Bogers M, Narayanan S, Rayan A, Alonso A, van der Meij J, Khamassi M, Khan ZU, Genzel L (2023) Increased cortical plasticity leads to memory interference and enhanced hippocampal-cortical interactions.eLife 12:e84911. doi: 10.7554/eLife.84911.
Navarro-Lobato I, Masmudi-Martín M, López-Aranda MF, López-Téllez JF, Delgado G, Granados-Durán P, Gaona-Romero C, Carretero-Rey M, Posadas S, Quiros-Ortega ME, Khan ZU (2024) Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer’s disease rodents.Neural Regeneration Research 19(8):1835-1841. doi: 10.4103/1673-5374.389301.
Masmudi-Martín M, Navarro-Lobato I, López-Aranda MF, Quiros-Ortega ME, Carretero-Rey M, Garcia-Garrido MF, López Téllez JF, Jiménez-Recuerda I, Muñoz de Leon López CA, Khan ZU (2024) Brain areas interconnected to ventral pathway circuits are independently able to induce enhancement in object recognition memory and cause reversal in object recognition memory deficit.CNS Neuroscience & Therapeutics 30(4):e14727. doi: 10.1111/cns.14727.
Muñoz de León-López CA, Carretero-Rey M, Khan ZU (2025) AMPA receptors in synaptic plasticity, memory function, and brain diseases.Cellular and Molecular Neurobiology 22;45(1):14. doi: 10.1007/s10571-024-01529-7.
Khan ZU, Carretero-Rey M, de León-López CAM, Navarro-Lobato I (2025) Memory-associated immediate early genes: roles in synaptic function, memory processes, and neurological diseases.Molecular Neurobiology 62(12):15885-15915. doi: 10.1007/s12035-025-05203-x.