Unbiased, High-Throughput Electron Microscopy Analysis of Experience-Dependent Synaptic Changes in the Neocortex.
نویسندگان
چکیده
UNLABELLED Neocortical circuits can be altered by sensory and motor experience, with experimental evidence supporting both anatomical and electrophysiological changes in synaptic properties. Previous studies have focused on changes in specific neurons or pathways-for example, the thalamocortical circuitry, layer 4-3 (L4-L3) synapses, or in the apical dendrites of L5 neurons- but a broad-scale analysis of experience-induced changes across the cortical column has been lacking. Without this comprehensive approach, a full understanding of how cortical circuits adapt during learning or altered sensory input will be impossible. Here we adapt an electron microscopy technique that selectively labels synapses, in combination with a machine-learning algorithm for semiautomated synapse detection, to perform an unbiased analysis of developmental and experience-dependent changes in synaptic properties across an entire cortical column in mice. Synapse density and length were compared across development and during whisker-evoked plasticity. Between postnatal days 14 and 18, synapse density significantly increases most in superficial layers, and synapse length increases in L3 and L5B. Removal of all but a single whisker row for 24 h led to an apparent increase in synapse density in L2 and a decrease in L6, and a significant increase in length in L3. Targeted electrophysiological analysis of changes in miniature EPSC and IPSC properties in L2 pyramidal neurons showed that mEPSC frequency nearly doubled in the whisker-spared column, a difference that was highly significant. Together, this analysis shows that data-intensive analysis of column-wide changes in synapse properties can generate specific and testable hypotheses about experience-dependent changes in cortical organization. SIGNIFICANCE STATEMENT Development and sensory experience can change synapse properties in the neocortex. Here we use a semiautomated analysis of electron microscopy images for an unbiased, column-wide analysis of synapse changes. This analysis reveals new loci for synaptic change that can be verified by targeted electrophysiological investigation. This method can be used as a platform for generating new hypotheses about synaptic changes across different brain areas and experimental conditions.
منابع مشابه
Unbiased, High-Throughput Electron Microscopy Analysis of Experience-Dependent Synaptic Changes
متن کامل
Pansynaptic Enlargement at Adult Cortical Connections Strengthened by Experience
Behavioral experience alters the strength of neuronal connections in adult neocortex. These changes in synaptic strength are thought to be central to experience-dependent plasticity, learning, and memory. However, it is not known how changes in synaptic transmission between neurons become persistent, thereby enabling the storage of previous experience. A long-standing hypothesis is that altered...
متن کاملP15: Hippocampus-Neocortical Communication in Learning
The hippocampus is located in the medial temporal lobe and is a part of the forebrain. It plays a critical role in formation of declared memories. The hippocampus is banana­-shaped and communicates with all parts of neocortex. Reptiles and birds have structures like hippocampus that potentially serve as navigation functions. During the mammalian evolution, the neocortex has a large expansio...
متن کاملEffects of visual deprivation on synaptic plasticity of visual cortex
TBS (Theta Burst Stimulation) and PBs (Primed Bursts) are among effective tetanic stimulations for induction of LTP in hippocampus. Recent studies have indicated that TBS is effective in LTP induction in layer III synapses of neocortex, only if applied to layer IV. However, the possibility of neocortical LTP induction using PBs, has not yet been investigated. Sensory deprivation greatly influ...
متن کاملGABA-mediated membrane oscillations as coincidence detectors for enhancing synaptic efficacy in the developing hippocampus
Spontaneously occurring neuronal oscillations constitute a hallmark of developmental networks. They have been observed in the retina, neocortex, hippocampus, thalamus and spinal cord. In the immature hippocampus the so-called ‘giant depolarizing potentials’ (GDPs) are network-driven membrane oscillations characterized by recurrent membrane depolarization with superimposed fast action potentials...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of neuroscience : the official journal of the Society for Neuroscience
دوره 35 50 شماره
صفحات -
تاریخ انتشار 2015