Publicação
Hippocampal time - The neural substrate of time in the memory system
| Resumo: | Episodic memory - the ability to recall specific past events within the context of space and time - is an integral part our daily lives and perhaps the most important computation attributed to the hippocampal system. While the spatial dimension of episodic memory has been widely researched many questions remain unanswered regarding its temporal aspect. Several studies have shown that hippocampus (HIPP) is able to encode the passage of time, retain information about sequences and organize memories in a temporal structure, playing a particularly important role in the temporal dimension of memory. However, the origin of timing signals in HIPP remains unclear and it is unknown whether the temporal firing patterns critically rely on upstream cortical input. The medial entorhinal cortex (MEC) is a major input and output structure of the HIPP and is commonly associated with spatial representation. However, recent studies have shown that entorhinal inputs to the HIPP are essential for bridging temporal gaps between associated events. Furthermore, there is recent evidence showing that time is also encoded in the firing rate of MEC’s principal cells. In this project, we have used an experimental paradigm that allowed us to test the processing of time independent of other behavioral variables, and in a goal-directed manner. The task, developed in the lab, is called Waiting to Trajectory task (WtT), and in it animals must use their ability to judge the duration of a temporal interval in order to get a reward. In order to test the involvement of MEC in the representation of temporal information, we used DREADDs, a viraldelivered modified muscarinic receptor responding to CNO, to silence MEC during WtT. Our results show that inactivating MEC results in decreased performance due to shorter waiting times. In the correct trials under CNO we observed longer waiting times. These results point to a critical function of MECHIPP circuitry in temporal coding accuracy. The results reported here informed present and future experimental plans running in the lab, aiming to dissect the mechanisms responsible for encoding the temporal dimension of episodic memory. |
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| Autores principais: | Ferreira, Raquel Filipa Rodrigues |
| Assunto: | Hipocampo Córtex entorrinal medial Tempo DREADDs Teses de mestrado - 2019 |
| Ano: | 2019 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Episodic memory - the ability to recall specific past events within the context of space and time - is an integral part our daily lives and perhaps the most important computation attributed to the hippocampal system. While the spatial dimension of episodic memory has been widely researched many questions remain unanswered regarding its temporal aspect. Several studies have shown that hippocampus (HIPP) is able to encode the passage of time, retain information about sequences and organize memories in a temporal structure, playing a particularly important role in the temporal dimension of memory. However, the origin of timing signals in HIPP remains unclear and it is unknown whether the temporal firing patterns critically rely on upstream cortical input. The medial entorhinal cortex (MEC) is a major input and output structure of the HIPP and is commonly associated with spatial representation. However, recent studies have shown that entorhinal inputs to the HIPP are essential for bridging temporal gaps between associated events. Furthermore, there is recent evidence showing that time is also encoded in the firing rate of MEC’s principal cells. In this project, we have used an experimental paradigm that allowed us to test the processing of time independent of other behavioral variables, and in a goal-directed manner. The task, developed in the lab, is called Waiting to Trajectory task (WtT), and in it animals must use their ability to judge the duration of a temporal interval in order to get a reward. In order to test the involvement of MEC in the representation of temporal information, we used DREADDs, a viraldelivered modified muscarinic receptor responding to CNO, to silence MEC during WtT. Our results show that inactivating MEC results in decreased performance due to shorter waiting times. In the correct trials under CNO we observed longer waiting times. These results point to a critical function of MECHIPP circuitry in temporal coding accuracy. The results reported here informed present and future experimental plans running in the lab, aiming to dissect the mechanisms responsible for encoding the temporal dimension of episodic memory. |
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