Local circuits in the olfactory bulb

项目摘要 神经科学中的一个中心问题是环境中的感觉刺激是如何表现出来的。嗅觉 系统是解决这个问题的一种有吸引力的感觉方式，因为主要的兴奋通路 连接嗅球的感受器神经元、二尖瓣细胞和嗅球的三级神经元 大脑皮层，而且很好理解。然而，细胞内的记录表明， 二级神经元(二尖瓣和簇状细胞)中的气味并不完全是来自 受体细胞。取而代之的是，嗅球的输出是兴奋和兴奋之间复杂的相互作用的结果。 和抑制电路。对产生抑制作用的神经回路的了解相对较少 主细胞。目前的方案使用啮齿动物脑片记录的方法来确定局部 电路通路兴奋GABA能嗅球间神经元，抑制和塑造大鼠的放电模式 主细胞。使用全细胞内记录和实时双光子成像方法，我们将 确定使感觉输入能够兴奋颗粒细胞的关键突触通路的功能和方式 它们在颗粒细胞内招募本征电流。该提案还将决定抑制性突触如何 颗粒细胞的输入起到调制动作电位放电的作用。最后，提出了本文的工作建议 将决定最近发现的一种形式的长期突触可塑性的功能作用 这些输入中的一类。确定产生感觉诱发抑制的细胞机制 嗅球是这项提案的总体重点，它对于理解生物信息是如何 在大脑中表现出来。拟议的研究也具有重要意义，因为它们代表着重要的一步 了解许多重大神经退行性疾病的特异性缺陷 功能受到影响。在许多这样的疾病中，感觉障碍发生在疾病发病的早期。 对这些疾病中影响的特定嗅觉机制的洞察可能导致直接测试 关于导致认知缺陷的大脑皮层类似机制的假说 通常与神经退行性疾病有关。

Project Summary A central question in neuroscience is how sensory stimuli in the environment are represented. The olfactory system is an attractive sensory modality to approach this question since the major excitatory pathways that connect receptor neurons, second-order mitral cells in the olfactory bulb, and tertiary neurons in olfactory cortex and well understood. However, intracellular recordings demonstrate that neural representations of odors in second-order neurons (mitral and tufted cells) do not result exclusively from feedforward input from receptor cells. Instead, the output of the olfactory bulb results from complex interactions between excitatory and inhibitory circuits. Relatively little is known about the neural circuits that generate inhibition onto principal cells. The present proposal uses rodent brain slice recording methods to determine how local circuit pathways excite GABAergic olfactory bulb interneurons, inhibiting and shaping firing patterns in principal cells. Using both whole-cell intracellular recording and live 2-photon imaging methods, we will determine how the key synaptic pathways that enable sensory input to excite granule cells function and how they recruit intrinsic currents within granule cells. The proposal also will determine how inhibitory synaptic input to granule cells functions to modulation action potential discharges. Finally, the proposed work also will determine the functional role of a recently discovered form of long-term synaptic plasticity apparent in one class of these inputs. Defining the cellular mechanisms that generate sensory-evoked inhibition in the olfactory bulb, the overall focus of this proposal, is critical to understand how biological information is represented in the brain. The proposed studies also are significant as they represent an important step toward understanding the specific deficits in many major neurodegenerative diseases in which olfactory function is affected. In many of these diseases, sensory impairments occur early in the disease onset. Insights into the specific olfactory mechanisms affected in these diseases may lead to directly testable hypotheses regarding analogous mechanisms in the cortical areas responsible for the cognitive deficits commonly associated with neurodegenerative disorders.