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| Author(s): |
Cleiton Lopes Aguiar
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2010-04-06 |
| Examining board members: |
João Pereira Leite;
Jorge Alberto Quillfeldt
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| Advisor: | João Pereira Leite |
| Abstract | |
The brain cholinergic system has a critical role in memory consolidation processes. Particularly, the medial prefrontal cortex (mPFC) shows an increase of acetylcholine (ACh) levels during and after memory tasks. Additionally, cholinergic muscarinic activation enhances long-term potentiation (LTP) and depression (LTD) in the hippocampus and cortex. We have recently demonstrated that muscarinic agonist pilocarpine (PILO) promotes an increase of the late-phase of LTP in the hippocampus-mPFC pathway associated with increases of rapid oscillations emergence in the hippocampus and cortex. Therefore, in the present work, we investigated the dynamic of cholinergic muscarinic modulation on LTD in the hippocampal-mPFC pathway and its glutamatergic neurotransmission dependence mediated by N-methyl-D-aspartate receptors (NMDAR). For this, urethane-anaesthetized rats under temperature body control (37±0,5ºC), were implanted with CA1 and mPFC microelectrodes for stimulation and recording of postsynaptic potentials (fPSP). After 30min of fPSP baseline recordings, LTD was induced by trains of electric pulses at low-frequency stimulation (LFS) and monitored for additional 240min. ln this protocol rats received either a microinjection of PILO (40nmol; 1µL, i.c.v.) or Veh (artificial cerebrospinal fluid, aCSF), immediately before or 20min after LFS. Beside this, in the order to assess the NMDAR role in the cortical LTD muscarinic modulation, a independent group of subjects received a selective NMDAR antagonist or vehicle (AP7; 20nmols; 0,4µL in NaCl 0,15M; intra-mPFC) 10min before PILO microinjection. Our results show that muscarinic pre-activation by PILO enhances the LTD in the CA1-mPFC pathway. However, PILO alone or applied 20min after LFS does not affect neither basal neurotransmission nor the late-phase of LTD in the CA1-mPFC. Also, the PILO preactivation effect on LTD is NMDAR-dependent, since the administration of AP7 inhibtis the cortical LTD maintenance. Thus, together with the data about muscarinic modulation of cortical LTP recently published by our laboratory, we suggest that muscarinic receptors activity is central to modulate the synaptic plasticity in a bidirectional way (LTP and LTD), depending of hippocampus CA1 firing rate. Because is one of the main information outflow from hippocampus to mPFC, studies about modulation of synaptic plasticity of CA1-mPFC pathway plasticity may provide new data about the mechanisms involved in the long-term consolidation of memories, the role of sleep on memory consolidation and about cognitive impairments in epilepsy, psychosis and psychiatry comorbidities. (AU) | |