RESUMO
Many brain diseases lead to a reduction in the number of functional neurons and it would be of value to be able to increase the number of neurons in the affected brain areas. In this study, we examined whether we can promote neural stem cells to produce mature neurons and whether an increase in the mature neurons can affect cognitive performance. We detected that the EphB2 receptor is localized in immature basolateral amygdala (BLA) neurons. We therefore aimed to increase the level of EphB2 activity in neural stem cells (NSCs) in the BLA and examine the effects on the production of mature neurons and cognition. Toward that end, we utilized a photoactivatable EphB2 construct (optoEphB2) to increase EphB2 forward signaling in NSCs in the BLA. We revealed that the activation of optoEphB2 in NSCs in the BLA increased the level of immature and mature neurons in the BLA. We further found that activation of optoEphB2 in BLA NSCs enhanced auditory, but not contextual, long-term fear memory formation. Impairing EphB2 forward signaling did not affect the level of immature and mature neurons in the BLA. This study provides evidence that NSCs can be promoted to produce mature neurons by activating EphB2 to enhance specific brain functions.
Assuntos
Complexo Nuclear Basolateral da Amígdala , Memória de Longo Prazo , Células-Tronco Neurais , Neurogênese , Receptor EphB2 , Animais , Receptor EphB2/metabolismo , Receptor EphB2/genética , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Memória de Longo Prazo/fisiologia , Masculino , Complexo Nuclear Basolateral da Amígdala/metabolismo , Complexo Nuclear Basolateral da Amígdala/citologia , Camundongos , Neurônios/metabolismo , Neurônios/citologia , Camundongos Endogâmicos C57BL , Medo/fisiologia , Transdução de SinaisRESUMO
Training rodents in a particularly difficult olfactory-discrimination (OD) task results in the acquisition of the ability to perform the task well, termed 'rule learning'. In addition to enhanced intrinsic excitability and synaptic excitation in piriform cortex pyramidal neurons, rule learning results in increased synaptic inhibition across the whole cortical network to the point where it precisely maintains the balance between inhibition and excitation. The mechanism underlying such precise inhibitory enhancement remains to be explored. Here, we use brain slices from transgenic mice (VGAT-ChR2-EYFP), enabling optogenetic stimulation of single GABAergic neurons and recordings of unitary synaptic events in pyramidal neurons. Quantal analysis revealed that learning-induced enhanced inhibition is mediated by increased quantal size of the evoked inhibitory events. Next, we examined the plasticity of synaptic inhibition induced by long-lasting, intrinsically evoked spike firing in post-synaptic neurons. Repetitive depolarizing current pulses from depolarized (-70 mV) or hyperpolarized (-90 mV) membrane potentials induced long-term depression (LTD) and long-term potentiation (LTP) of synaptic inhibition, respectively. We found a profound bidirectional increase in the ability to induce both LTD, mediated by L-type calcium channels, and LTP, mediated by R-type calcium channels after rule learning. Blocking the GABAB receptor reversed the effect of intrinsic stimulation at -90 mV from LTP to LTD. We suggest that learning greatly enhances the ability to modify the strength of synaptic inhibition of principal neurons in both directions. Such plasticity of synaptic plasticity allows fine-tuning of inhibition on each particular neuron, thereby stabilizing the network while maintaining the memory of the rule. KEY POINTS: Olfactory discrimination rule learning results in long-lasting enhancement of synaptic inhibition on piriform cortex pyramidal neurons. Quantal analysis of unitary inhibitory synaptic events, evoked by optogenetic minimal stimulation, revealed that enhanced synaptic inhibition is mediated by increased quantal size. Surprisingly, metaplasticity of synaptic inhibition, induced by intrinsically evoked repetitive spike firing, is increased bidirectionally. The susceptibility to both long-term depression (LTD) and long-term potentiation (LTP) of inhibition is enhanced after learning. LTD of synaptic inhibition is mediated by L-type calcium channels and LTP by R-type calcium channels. LTP is also dependent on activation of GABAB receptors. We suggest that learning-induced changes in the metaplasticity of synaptic inhibition enable the fine-tuning of inhibition on each particular neuron, thereby stabilizing the network while maintaining the memory of the rule.
Assuntos
Camundongos Transgênicos , Plasticidade Neuronal , Células Piramidais , Animais , Plasticidade Neuronal/fisiologia , Camundongos , Células Piramidais/fisiologia , Neurônios GABAérgicos/fisiologia , Aprendizagem/fisiologia , Potenciação de Longa Duração/fisiologia , Masculino , Sinapses/fisiologia , Optogenética , Inibição Neural/fisiologia , Córtex Piriforme/fisiologia , Camundongos Endogâmicos C57BL , Depressão Sináptica de Longo Prazo/fisiologiaRESUMO
This paper presents a measurement setup which is able to measure the distribution of small scale pressure on an area of 15.2â¯mm × 30.4â¯mm with a sample rate up to 1.2â¯kHz. It was used to investigate the contact pressures of vocal folds during phonation. This was performed in ex vivo experiments of 11 porcine larynges. The contact pressure at the medial surface and other phonation parameters, as the glottal resistance and the closing velocity of the vocal fold, were measured at different adduction and elongation levels and air flow rates. A statistical analysis was carried out. It could be shown that the contact pressure rises, when the vocal fold is manipulated or when the flow rate is increased.