scholarly journals Comprehensive imaging of synaptic activity reveals dendritic growth rules that cluster inputs

2021 ◽  
Author(s):  
Kaspar Podgorski ◽  
Tristan Dellazizzo Toth ◽  
Patrick Coleman ◽  
Serhiy Opushnyev ◽  
Janaina Brusco ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Dendritic Growth ◽  
Sensory Input ◽  
Random Access ◽  
Synaptic Activity ◽  
Synaptic Inputs ◽  
Neural Computations ◽  
Dendritic Arbors ◽  
Evoked Activity ◽  
Developing Neurons

AbstractThe distribution of synapses across dendritic arbors determines their contribution to neural computations since nonlinear conductances amplify co-active clustered inputs. To determine whether, and how patterned synaptic topography arises during development we developed a random-access microscope capable of full-neuron calcium imaging of activity and structural plasticity of developing neurons in awake Xenopus tadpoles. By imaging growing brain neurons in response to plasticity-inducing visual training, we show coordinated growth and synaptogenesis specific to each neuron’s spike tuning. High evoked activity in neurons tuned to the trained stimulus induced pruning of non-driven inputs across the dendritic arbor as these neurons strengthened their responses to this stimulus. In stark contrast, initially unresponsive neurons that shifted their spike tuning toward the trained stimulus exhibited localized growth and new responsive synapses near existing active inputs. These information-driven growth rules promote clustering of synapses tuned to a developing neuron’s emerging receptive field.One-Sentence SummarySensory input directs brain neuronal growth and connectivity promoting clustering of synaptic inputs tuned to a neuron’s encoding properties.

Developmental regulation of plasticity in cat somatosensory cortex

1994 ◽  
Vol 72 (4) ◽  
pp. 1706-1716 ◽  
Author(s):  
S. L. Juliano ◽  
D. E. Eslin ◽  
M. Tommerdahl
Keyword(s):  
Somatosensory Cortex ◽  
Sensory Input ◽  
Developmental Regulation ◽  
Normal Pattern ◽  
Metabolic Pattern ◽  
Somatosensory Cortices ◽  
Experimental Side ◽  
Adult Cats ◽  
Evoked Activity ◽  
The Individual

1. The neocortical response to deprivation of somatic sensory input in young animals of different ages was compared with the same manipulation in adults. The response was measured through the use of 2-deoxyglucose (2DG) mapping. Although several features of the cortical response were similar in animals of all ages, the metabolic patterns evoked by somatic stimulation differed substantially from each other at all ages. 2. When adult cats receive a digit amputation and survive from 2 to 8 wk, the pattern of stimulus-evoked metabolic uptake expands dramatically in the somatosensory cortex contralateral to the deprived forepaw. Comparisons between the normal and experimental somatosensory cortices reveal that the distribution of activity on the experimental side was roughly an expanded version of the normal pattern. 3. Unilateral digit amputations of digit 2 were conducted on kittens 2, 4, or 6 wk old. They survived until 3–4 mo and then received a 2DG experiment, during which digit 3 was stimulated bilaterally. Evaluation of the evoked metabolic pattern indicated substantial differences from the activity elicited in adults undergoing identical manipulations. 4. The individual patches of activity that made up the metabolic pattern were similar in intensity in both hemispheres when the digit amputation was conducted at either 2, 4, or 6 wk. After a digit amputation at 2 wk, the patches were significantly narrower in the experimental hemisphere; after a digit amputation at 6 wk, the patches were significantly wider in the hemisphere receiving from the deprived forepaw. 5. Two-dimensional maps of 2DG uptake in areas 3b and 1 of the somatosensory cortex reveal that after a digit amputation at 2, 4, or 6 wk, the distribution of activity in the hemisphere receiving from the digit amputation was more dispersed and widespread than in the normal hemisphere. The dispersed pattern of uptake was not an expanded version of the normal pattern, but scattered over a wider region of somatosensory cortex. This observation is similar to the normal pattern of evoked activity seen in developing animals. 6. The total area of 2DG uptake in the somatosensory cortex contralateral to a digit amputation conducted at 2 or 4 wk was not greater than that in the normal hemisphere, even though it was more widespread. After a digit amputation at 6 wk, however, the area of evoked activity was greater in the experimental hemisphere but not of the magnitude as the same manipulation in an adult.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Spontaneous activations follow a common developmental course across primary sensory areas in mouse neocortex

2016 ◽  
Vol 116 (2) ◽  
pp. 431-437 ◽  
Author(s):  
Charles G. Frye ◽  
Jason N. MacLean
Keyword(s):  
Calcium Imaging ◽  
Sensory Input ◽  
Primary Auditory Cortex ◽  
Developmental Trajectory ◽  
Two Photon ◽  
Developmental Progression ◽  
Sensory Modalities ◽  
Spatially Distributed ◽  
And Function ◽  
Insight Into

Spontaneous propagation of spiking within the local neocortical circuits of mature primary sensory areas is highly nonrandom, engaging specific sets of interconnected and functionally related neurons. These spontaneous activations promise insight into neocortical structure and function, but their properties in the first 2 wk of perinatal development are incompletely characterized. Previously, we have found that there is a minimal numerical sample, on the order of 400 cells, necessary to fully capture mature neocortical circuit dynamics. Therefore we maximized our numerical sample by using two-photon calcium imaging to observe spontaneous activity in populations of up to 1,062 neurons spanning multiple columns and layers in 52 acute coronal slices of mouse neocortex at each day from postnatal day (PND) 3 to PND 15. Slices contained either primary auditory cortex (A1) or somatosensory barrel field (S1BF), which allowed us to compare sensory modalities with markedly different developmental timelines. Between PND 3 and PND 8, populations in both areas exhibited activations of anatomically compact subgroups on the order of dozens of cells. Between PND 9 and PND 13, the spatiotemporal structure of the activity diversified to include spatially distributed activations encompassing hundreds of cells. Sparse activations covering the entire field of view dominated in slices taken on or after PND 14. These and other findings demonstrate that the developmental progression of spontaneous activations from active local modules in the first postnatal week to sparse, intermingled groups of neurons at the beginning of the third postnatal week generalizes across primary sensory areas, consistent with an intrinsic developmental trajectory independent of sensory input.

scholarly journals Development of Spontaneous Miniature EPSCs in Mouse AVCN Neurons During a Critical Period of Afferent-Dependent Neuron Survival

2007 ◽  
Vol 97 (1) ◽  
pp. 635-646 ◽  
Author(s):  
Yong Lu ◽  
Julie A. Harris ◽  
Edwin W. Rubel
Keyword(s):  
Critical Period ◽  
Stellate Cells ◽  
Synaptic Activity ◽  
Developmental Changes ◽  
Synaptic Inputs ◽  
Whole Cell Patch Clamp ◽  
Bushy Cell ◽  
Anteroventral Cochlear Nucleus ◽  
Decay Times ◽  
Bushy Cells

During a critical period prior to hearing onset, cochlea ablation leads to massive neuronal death in the mouse anteroventral cochlear nucleus (AVCN), where cell survival is believed to depend on glutamatergic input. We investigated the development of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in AVCN neurons using whole cell patch-clamp techniques during [postnatal day 7 (P7)] and after (P14, P21) this critical period. We also examined the effects of unilateral cochlea ablation on mEPSC development. The two main AVCN neuron types, bushy and stellate cells, were distinguished electrophysiologically. Bushy cell mEPSCs became more frequent and faster between P7 and P14/P21 but with little change in amplitude. Dendritic filtering of mEPSCs was not detected as indicated by the lack of correlation between 10 and 90% rise times and decay time constants. Seven days after cochlea ablation at P7 or P14, mEPSCs in surviving bushy cells were similar to controls, except that rise and decay times were positively correlated ( R = 0.31 and 0.14 for surgery at P7 and P14, respectively). Consistent with this evidence for a shift of synaptic activity from the somata to the dendrites, SV2 staining (a synaptic vesicle marker) forms a ring around somata of control but not experimental bushy cells. In contrast, mEPSCs of stellate cells showed few significant changes over these ages with or without cochlea ablation. Taken together, mEPSCs in mouse AVCN bushy cells show dramatic developmental changes across this critical period, and cochlea ablation may lead to the emergence of excitatory synaptic inputs impinging on bushy cell dendrites.

Propagation of action potentials in the dendrites of neurons from rat spinal cord slice cultures

1996 ◽  
Vol 75 (1) ◽  
pp. 154-170 ◽  
Author(s):  
M. E. Larkum ◽  
M. G. Rioult ◽  
H. R. Luscher
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Calcium Imaging ◽  
Action Potentials ◽  
Synaptic Activity ◽  
Rat Spinal Cord ◽  
Voltage Sensitive Dye ◽  
Single Action ◽  
Before And After ◽  
Time Courses

1. We examined the propagation of action potentials in the dendrites of ventrally located presumed motoneurons of organotypic rat spinal cord cultures. Simultaneous patch electrode recordings were made from the dendrites and somata of individual cells. In other experiments we visualized the membrane voltage over all the proximal dendrites simultaneously using a voltage-sensitive dye and an array of photodiodes. Calcium imaging was used to measure the dendritic rise in Ca2+ accompanying the propagating action potentials. 2. Spontaneous and evoked action potentials were recorded using high-resistance patch electrodes with separations of 30-423 microm between the somatic and dendritic electrodes. 3. Action potentials recorded in the dendrites varied considerably in amplitude but were larger than would be expected if the dendrites were to behave as passive cables (sometimes little or no decrement was seen for distances of > 100 microm). Because the amplitude of the action potentials in different dendrites was not a simple function of distance from the soma, we suggest that the conductance responsible for the boosting of the action potential amplitude varied in density from dendrite to dendrite and possibly along each dendrite. 4. The dendritic action potentials were usually smaller and broader and arrived later at the dendritic electrode than at the somatic electrode irrespective of whether stimulation occurred at the dendrite or soma or as a result of spontaneous synaptic activity. This is clear evidence that the action potential is initiated at or near the soma and spreads out into the dendrites. The conduction velocity of the propagating action potential was estimated to be 0.5 m/s. 5. The voltage time courses of previously recorded action potentials were generated at the soma using voltage clamp before and after applying 1 microM tetrodotoxin (TTX) over the soma and dendrites. TTX reduced the amplitude of the action potential at the dendritic electrode to a value in the range expected for dendrites that behave as passive cables. This indicates that the conductance responsible for the actively propagating action potentials is a Na+ conductance. 6. The amplitude of the dendritic action potential could also be initially reduced more than the somatic action potential using 1-10 mM QX-314 (an intracellular sodium channel blocker) in the dendritic electrode as the drug diffused from the dendritic electrode toward the soma. Furthermore, in some cases the action potential elicited by current injection into the dendrite had two components. The first component was blocked by QX-314 in the first few seconds of the diffusion of the blocker. 7. In some cells, an afterdepolarizing potential (ADP) was more prominent in the dendrite than in the soma. This ADP could be reversibly blocked by 1 mM Ni2+ or by perfusion of a nominally Ca2+-free solution over the soma and dendrites. This suggests that the back-propagating action potential caused an influx of Ca2+ predominantly in the dendrites. 8. With the use of a voltage-sensitive dye (di-8-ANEPPS) and an array of photodiodes, the action potential was tracked along all the proximal dendrites simultaneously. The results confirmed that the action potential propagated actively, in contrast to similarly measured hyperpolarizing pulses that spread passively. There were also indications that the action potential was not uniformly propagated in all the dendrites, suggesting the possibility that the distribution of Na+ channels over the dendritic membrane is not uniform. 9. Calcium imaging with the Ca2+ fluorescent indicator Fluo-3 showed a larger percentage change in fluorescence in the dendrites than in the soma. Both bursts and single action potentials elicited sharp rises in fluorescence in the proximal dendrites, suggesting that the back-propagating action potential causes a concomitant rise in intracellular calcium concentration...

scholarly journals Reversed synaptic effects of hypocretin and NPY mediated by excitatory GABA-dependent synaptic activity in developing MCH neurons

2013 ◽  
Vol 109 (6) ◽  
pp. 1571-1578 ◽  
Author(s):  
Ying Li ◽  
Youfen Xu ◽  
Anthony N. van den Pol
Keyword(s):  
Energy Homeostasis ◽  
Fluorescent Protein ◽  
Gaba Release ◽  
Synaptic Activity ◽  
Sodium Calcium Exchanger ◽  
Inhibitory Neurotransmitter ◽  
Mature Neurons ◽  
Excitatory Gaba ◽  
Green Fluorescent ◽  
Developing Neurons

In mature neurons, GABA is the primary inhibitory neurotransmitter. In contrast, in developing neurons, GABA exerts excitatory actions, and in some neurons GABA-mediated excitatory synaptic activity is more prevalent than glutamate-mediated excitation. Hypothalamic neuropeptides that modulate cognitive arousal and energy homeostasis, hypocretin/orexin and neuropeptide Y (NPY), evoked reversed effects on synaptic actions that were dependent on presynaptic GABA release onto melanin-concentrating hormone (MCH) neurons. MCH neurons were identified by selective green fluorescent protein (GFP) expression in transgenic mice. In adults, hypocretin increased GABA release leading to reduced excitation. In contrast, in the developing brain as studied here with analysis of miniature excitatory postsynaptic currents, paired-pulse ratios, and evoked potentials, hypocretin acted presynaptically to enhance the excitatory actions of GABA. The ability of hypocretin to enhance GABA release increases inhibition in adult neurons but paradoxically enhances excitation in developing MCH neurons. In contrast, NPY attenuation of GABA release reduced inhibition in mature neurons but enhanced inhibition during development by attenuating GABA excitation. Both hypocretin and NPY also evoked direct actions on developing MCH neurons. Hypocretin excited MCH cells by activating a sodium-calcium exchanger and by reducing potassium currents; NPY reduced activity by increasing an inwardly rectifying potassium current. These data for the first time show that both hypocretin and NPY receptors are functional presynaptically during early postnatal hypothalamic development and that both neuropeptides modulate GABA actions during development with a valence of enhanced excitation or inhibition opposite to that of the adult state, potentially allowing neuropeptide modulation of use-dependent synapse stabilization.

scholarly journals Coordinated cerebellar climbing fiber activity signals learned sensorimotor predictions

2018 ◽  
Author(s):  
William Heffley ◽  
Eun Young Song ◽  
Ziye Xu ◽  
Benjamin N. Taylor ◽  
Mary Anne Hughes ◽  
...  
Keyword(s):  
Reinforcement Learning ◽  
Motor Learning ◽  
Calcium Imaging ◽  
Sensory Input ◽  
Activity Patterns ◽  
Motor Output ◽  
Neural Pathways ◽  
Learning Paradigm ◽  
Correlated Activity ◽  
Task Parameters

AbstractThe prevailing model of cerebellar learning states that climbing fibers (CFs) are both driven by, and serve to correct, erroneous motor output. However, this model is grounded largely in studies of behaviors that utilize hardwired neural pathways to link sensory input to motor output. To test whether this model applies to more flexible learning regimes that require arbitrary sensorimotor associations, we have developed a cerebellar-dependent motor learning paradigm compatible with both mesoscale and single dendrite resolution calcium imaging in mice. Here, we find that CFs are preferentially driven by and more time-locked to correctly executed movements and other task parameters that predict reward outcome, exhibiting widespread correlated activity within parasagittal processing zones that is governed by these predictions. Together, such CF activity patterns are well-suited to drive learning by providing predictive instructional input consistent with an unsigned reinforcement learning signal that does not rely exclusively on motor errors.

scholarly journals Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits

2018 ◽  
Author(s):  
D Barson ◽  
AS Hamodi ◽  
X Shen ◽  
G Lur ◽  
RT Constable ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Spatial Scales ◽  
Cortical Circuits ◽  
Orthogonal Axis ◽  
Two Photon ◽  
Evoked Activity ◽  
Sensory Evoked ◽  
Local Circuits ◽  
The Brain ◽  
Juvenile Mouse

AbstractSpontaneous and sensory-evoked activity propagates across spatial scales in the mammalian cortex but technical challenges have generally precluded establishing conceptual links between the function of local circuits of neurons and brain-wide network dynamics. To solve this problem, we developed a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake, behaving mice. Our method employs an orthogonal axis design whereby the mesoscopic objective is oriented downward directly above the brain and the two-photon objective is oriented horizontally, with imaging performed through a glass right angle microprism implanted in the skull. In support of this method, we introduce a suite of analysis tools for relating the activity of individual cells to distal cortical areas, as well as a viral method for robust and widespread gene delivery in the juvenile mouse brain. We use these methods to characterize the diversity of associations of individual, genetically-defined neurons with cortex-wide network motifs.

scholarly journals Model-based decoupling of evoked and spontaneous neural activity in calcium imaging data

2020 ◽  
Vol 16 (11) ◽  
pp. e1008330
Author(s):  
Marcus A. Triplett ◽  
Zac Pujic ◽  
Biao Sun ◽  
Lilach Avitan ◽  
Geoffrey J. Goodhill
Keyword(s):  
Spontaneous Activity ◽  
Neural Activity ◽  
Calcium Imaging ◽  
Temporal Dynamics ◽  
Population Level ◽  
Imaging Data ◽  
Evoked Activity ◽  
Zebrafish Optic Tectum ◽  
Low Dimensional ◽  
Mouse Visual Cortex

The pattern of neural activity evoked by a stimulus can be substantially affected by ongoing spontaneous activity. Separating these two types of activity is particularly important for calcium imaging data given the slow temporal dynamics of calcium indicators. Here we present a statistical model that decouples stimulus-driven activity from low dimensional spontaneous activity in this case. The model identifies hidden factors giving rise to spontaneous activity while jointly estimating stimulus tuning properties that account for the confounding effects that these factors introduce. By applying our model to data from zebrafish optic tectum and mouse visual cortex, we obtain quantitative measurements of the extent that neurons in each case are driven by evoked activity, spontaneous activity, and their interaction. By not averaging away potentially important information encoded in spontaneous activity, this broadly applicable model brings new insight into population-level neural activity within single trials.

scholarly journals Robot-Embodied Neuronal Networks as an Interactive Model of Learning

2017 ◽  
Vol 11 (1) ◽  
pp. 39-47
Author(s):  
Abraham M Shultz ◽  
Sangmook Lee ◽  
Mary Guaraldi ◽  
Thomas B. Shea ◽  
Holly A. Yanco
Keyword(s):  
Cortical Neurons ◽  
Neuronal Networks ◽  
Sensory Input ◽  
Ex Vivo ◽  
Neuronal Cell ◽  
Motor Output ◽  
Synaptic Activity ◽  
Abnormal Development ◽  
Electrode Arrays ◽  
Complex Signals

Background and Objective:The reductionist approach of neuronal cell culture has been useful for analyses of synaptic signaling. Murine cortical neurons in culture spontaneously form anex vivonetwork capable of transmitting complex signals, and have been useful for analyses of several fundamental aspects of neuronal development hitherto difficult to clarifyin situ. However, these networks lack the ability to receive and respond to sensory input from the environment as do neuronsin vivo. Establishment of these networks in culture chambers containing multi-electrode arrays allows recording of synaptic activity as well as stimulation.Method:This article describes the embodiment ofex vivoneuronal networks neurons in a closed-loop cybernetic system, consisting of digitized video signals as sensory input and a robot arm as motor output.Results:In this system, the neuronal network essentially functions as a simple central nervous system. This embodied network displays the ability to track a target in a naturalistic environment. These findings underscore thatex vivoneuronal networks can respond to sensory input and direct motor output.Conclusion:These analyses may contribute to optimization of neuronal-computer interfaces for perceptive and locomotive prosthetic applications.Ex vivonetworks display critical alterations in signal patterns following treatment with subcytotoxic concentrations of amyloid-beta. Future studies including comparison of tracking accuracy of embodied networks prepared from mice harboring key mutations with those from normal mice, accompanied with exposure to Abeta and/or other neurotoxins, may provide a useful model system for monitoring subtle impairment of neuronal function as well as normal and abnormal development.

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