78 research outputs found
Cholinergic Activation of M2 Receptors Leads to Context-Dependent Modulation of Feedforward Inhibition in the Visual Thalamus
The temporal dynamics of inhibition within a neural network is a crucial determinant of information processing. Here, the authors describe in the visual thalamus how neuromodulation governs the magnitude and time course of inhibition in an input-dependent way
A biophysical model of endocannabinoid-mediated short term depression in hippocampal inhibition
Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The
plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis
of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread
action on brain function through modulation of synap–tic transmission and plasticity. Recent experimental studies have
characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain
regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and
memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and
investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI), a prominent form of shortterm
synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key
characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical
description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to
test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked.
The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit
DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing
rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate
experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a
stepping stone for future deciphering of the role of endocannabinoids in synaptic transmission as a feedback mechanism
both at synaptic and network level
Selective Cholinergic Depletion in Medial Septum Leads to Impaired Long Term Potentiation and Glutamatergic Synaptic Currents in the Hippocampus
Cholinergic depletion in the medial septum (MS) is associated with impaired hippocampal-dependent learning and memory. Here we investigated whether long term potentiation (LTP) and synaptic currents, mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the CA1 hippocampal region, are affected following cholinergic lesions of the MS. Stereotaxic intra-medioseptal infusions of a selective immunotoxin, 192-saporin, against cholinergic neurons or sterile saline were made in adult rats. Four days after infusions, hippocampal slices were made and LTP, whole cell, and single channel (AMPA or NMDA receptor) currents were recorded. Results demonstrated impairment in the induction and expression of LTP in lesioned rats. Lesioned rats also showed decreases in synaptic currents from CA1 pyramidal cells and synaptosomal single channels of AMPA and NMDA receptors. Our results suggest that MS cholinergic afferents modulate LTP and glutamatergic currents in the CA1 region of the hippocampus, providing a potential synaptic mechanism for the learning and memory deficits observed in the rodent model of selective MS cholinergic lesioning
Relatório de estágio em farmácia comunitária
Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr
Differences between presynaptic and postsynaptic GABAB mechanisms in rat hippocampal pyramidal cells
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