scholarly journals Hippocampal neurons with stable excitatory connectivity become part of neuronal representations

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000928 ◽  
Author(s):  
Tim P. Castello-Waldow ◽  
Ghabiba Weston ◽  
Alessandro F. Ulivi ◽  
Alireza Chenani ◽  
Yonatan Loewenstein ◽  
...  

Experiences are represented in the brain by patterns of neuronal activity. Ensembles of neurons representing experience undergo activity-dependent plasticity and are important for learning and recall. They are thus considered cellular engrams of memory. Yet, the cellular events that bias neurons to become part of a neuronal representation are largely unknown. In rodents, turnover of structural connectivity has been proposed to underlie the turnover of neuronal representations and also to be a cellular mechanism defining the time duration for which memories are stored in the hippocampus. If these hypotheses are true, structural dynamics of connectivity should be involved in the formation of neuronal representations and concurrently important for learning and recall. To tackle these questions, we used deep-brain 2-photon (2P) time-lapse imaging in transgenic mice in which neurons expressing the Immediate Early Gene (IEG) Arc (activity-regulated cytoskeleton-associated protein) could be permanently labeled during a specific time window. This enabled us to investigate the dynamics of excitatory synaptic connectivity—using dendritic spines as proxies—of hippocampal CA1 (cornu ammonis 1) pyramidal neurons (PNs) becoming part of neuronal representations exploiting Arc as an indicator of being part of neuronal representations. We discovered that neurons that will prospectively express Arc have slower turnover of synaptic connectivity, thus suggesting that synaptic stability prior to experience can bias neurons to become part of representations or possibly engrams. We also found a negative correlation between stability of structural synaptic connectivity and the ability to recall features of a hippocampal-dependent memory, which suggests that faster structural turnover in hippocampal CA1 might be functional for memory.

2019 ◽  
Author(s):  
Tim P. Castello-Waldow ◽  
Ghabiba Weston ◽  
Alireza Chenani ◽  
Yonatan Loewenstein ◽  
Alon Chen ◽  
...  

SUMMARYNeurons undergoing activity-dependent plasticity represent experience and are functional for learning and recall thus they are considered cellular engrams of memory. Although increase in excitability and stability of structural synaptic connectivity have been implicated in the formation and persistance of engrams, the mechanisms bringing engrams into existence are still largely unknown. To investigate this issue, we tracked the dynamics of structural excitatory synaptic connectivity of hippocampal CA1 pyramidal neurons over two weeks using deep-brain two-photon imaging in live mice. We found that neurons that will prospectively become part of an engram display higher stability of connectivity than neurons that will not. A novel experience significantly stabilizes the connectivity of non-engram neurons. Finally, the density and survival of dendritic spines negatively correlates to freezing to the context but not to the tone in a trace fear conditioning learning paradigm.


Author(s):  
Longjia Chu ◽  
Baihe Zhu ◽  
T. F. Fwa

Overnight repairs and resurfacing of runway or taxiway pavements are common in busy airports. The time window available for such repair and resurfacing works is often limited. A common problem encountered is to ensure that the newly compacted asphalt mixture has cooled down sufficiently before receiving aircraft loadings, so as to avoid premature deformation and failure of the asphalt mixture. In this regard, a simulation model that provides a prediction of the temperature–time variation trend of each compacted pavement lift in a multi-lift asphalt course laying would be a valuable planning tool for temperature control. Information on the temperature cooling trend of an asphalt layer helps to estimate the time duration available for effective compaction during laying, as well as the time lapse needed before the pavement is sufficiently stable to receive traffic. A finite element simulation model is presented in this study to predict the temperature–time variation trends of successive asphalt lifts in a multi-lift asphalt mixture laying operation. The numerical model was developed based on the theory of thermodynamics taking into account the heat transfer effects of solar radiation, convection, and conduction. The model was calibrated and validated using data from a field trial involving a two-lift and a three-lift laying of asphalt mixtures. Illustrative examples are presented to demonstrate the applications of the simulation model as a temperature control planning tool for repair and resurfacing operations of airport pavements.


2016 ◽  
Vol 68 (3) ◽  
pp. 567-573
Author(s):  
Yu Zheng ◽  
Lei Dong ◽  
Ying Kong ◽  
Hui Hong ◽  
Yang Gao ◽  
...  

Transcranial magnetic stimulation (TMS) has proven to be an invaluable tool both in clinical practice and basic brain research. However, many concomitant effects of TMS are still incompletely understood, including thermal effects induced by TMS. The present study investigated how thermal effects induced by magnetic stimulation influence the properties of the spontaneous excitatory postsynaptic current (sEPSC) of hippocampal CA1 pyramidal neurons. We have demonstrated that a 50-Hz low-frequency electromagnetic field with intensities of 7, 14, and 23 mT can induce thermal heating in artificial cerebrospinal fluid(aCSF) from 25 to 40?C over a period of 15 min. We also report that the thermal effects induced by TMS directly influence the properties of sEPSC in hippocampal CA1 pyramidal neurons. Double measures were taken to control the temperature across experiments in order to ensure the accuracy of the temperature measurement of the aCSF. These novel findings provide important insight into the thermal effects induced by TMS as well as their consequences.


1996 ◽  
Vol 76 (5) ◽  
pp. 2896-2906 ◽  
Author(s):  
H. Tsubokawa ◽  
W. N. Ross

1. We studied the effects of synaptic inhibition on backpropagating Na+ spikes in the apical dendrites of CA1 pyramidal neurons in transverse slices from the rat hippocampus. Action potentials were evoked synaptically by stimulation in the stratum radiatum or antidromically by stimulation in the alveus. 2. Inhibitory postsynaptic potentials, evoked by stimulation in the stratum lacunosum moleculare, reduced the amplitude of single spikes in the distal dendrites but did not change the amplitudes in the somatic or proximal regions. Inhibition also reduced the spike-associated [Ca2+]i changes in the distal dendrites but had little effect on the changes in the proximal part of the cell. Both of these results are consistent with inhibition converting actively backpropagating spikes into passively spreading potentials at some point in the arbor. 3. In most cells, the spike amplitude reduction in the distal dendrites was blocked by bicuculline methiodide (10 microM) and inhibition was most effective when evoked in a time window < 10 ms preceding the action potential. This suggests that the amplitude reduction was due to a conductance shunt activated by gamma-aminobuturic acid-A (GABAA) receptors. Synaptically evoked GABAB responses were detected but usually did not block spike propagation. 4. Direct hyperpolarization in the distal dendrites was also effective in blocking antidromically evoked spike backpropagation but probably does not contribute when the action potentials are evoked synaptically. 5. This effect of inhibition is different from its usual function in synaptic integration because spike generation and propagation down the axon are not significantly affected. This kind of inhibition might be important in regulating transient [Ca2+]i changes in the dendrites including individual dendritic branches.


1995 ◽  
Vol 74 (3) ◽  
pp. 1028-1036 ◽  
Author(s):  
H. Ishibashi ◽  
N. Akaike

1. The effects of somatostatin (SS) on the low-voltage-activated and high-voltage-activated (HVA) Ca2+ channels in pyramidal neurons acutely dissociated from the hippocampal CA1 region of 2- to 3-wk-old rats were investigated in a nystatin perforated-patch recording configuration under voltage-clamp conditions. 2. SS had no effect on the low-voltage-activated Ca2+ channel but did inhibit the HVA Ca2+ channel in a concentration-, time-, and voltage-dependent manner. 3. SS showed the activation phase of Ba2+ current (IBa) passing through HVA Ca2+ channels, and the maximum inhibition was 28% of the total current amplitude measured 10 ms after the current activation. The inhibitory effect was eliminated by applying larger depolarizing prepulses. Pretreatment with pertussis toxin (PTX) completely blocked the effect of SS on HVA IBa, suggesting the contribution of PTX-sensitive Gi/Go proteins to the SS-induced inhibition. 4. The applications of forskolin, 8-Br-cAMP, dibutyryl-guanosine 3'5'-cyclic monophosphate, staurosporine, and 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine did not affect either the control HVA IBa or the SS-induced inhibition of HVA IBa. 5. Pretreatment with protein kinase C (PKC) activators had no significant effect on HVA IBa but did remove the inhibition of HVA IBa by SS. 6. Omega-Conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega-conotoxin-MVIIC blocked HVA IBa by 27, 13, 38, and 9% of the total HVA current, respectively, which suggested the existence of N-, P-, L-, and Q-type HVA Ca2+ channels in the hippocampal CA1 pyramidal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)


2019 ◽  
Author(s):  
Laura Tapella ◽  
Teresa Soda ◽  
Lisa Mapelli ◽  
Valeria Bortolotto ◽  
Heather Bondi ◽  
...  

ABSTRACTAstrocytes perform important housekeeping functions in the nervous system including maintenance of adequate neuronal excitability, although the regulatory mechanisms are currently poorly understood. The astrocytic Ca2+/calmodulin-activated phosphatase calcineurin (CaN) is implicated in the development of reactive gliosis and neuroinflammation, but its roles, including the control of neuronal excitability, in healthy brain is unknown. We have generated a mouse line with conditional knockout (KO) of CaN B1 (CaNB1) in glial fibrillary acidic protein (GFAP)-expressing astrocytes (astroglial calcineurin knock-out, ACN-KO). Here we report that postnatal and astrocyte-specific ablation of CaNB1 did not alter normal growth and development as well as adult neurogenesis. Yet, we found that specific deletion of astrocytic CaN selectively impairs intrinsic neuronal excitability in hippocampal CA1 pyramidal neurons and cerebellar granule cells (CGCs). This impairment was associated with a decrease in after-hyperpolarization in CGC, while passive properties were unchanged, suggesting impairment of K+ homeostasis. Indeed, blockade of Na+/K+-ATPase (NKA) with ouabain phenocopied the electrophysiological alterations observed in ACN-KO CGCs. In addition, NKA activity was significantly lower in cerebellar and hippocampal lysates and in pure astrocytic cultures from ACN-KO mice. While no changes were found in protein levels, NKA activity was inhibited by the specific CaN inhibitor FK506 in both cerebellar lysates and primary astroglia from control mice, suggesting that CaN directly modulates NKA activity and in this manner controls neuronal excitability. In summary, our data provide formal evidence for the notion that astroglia is fundamental for controlling basic neuronal functions and place CaN center-stage as an astrocytic Ca2+-sensitive switch.


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