Intracellular Calcium Waves Transmit Synaptic Information to the Nucleus in Hippocampal Pyramidal Neurons

Yeckel, Mark F.; Sleeper, Amanda A.; Fitzpatrick, John S.; Hertle, Daniel N.; Hagenston, Anna M.; Garner, Robin T.

doi:10.1007/978-0-387-73609-9_4

Cited by 3 publications

(3 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given the robustness of internal Ca 2+ release compared to VGCC‐mediated rises (see Fig. 1) and the ease with which it can be elicited (as few as 2–3 stimulation pulses can evoke intracellular Ca 2+ waves; Nakamura et al 1999; Kapur et al 2001; Yeckel et al 2008), we believe that Ca 2+ release is likely to play an important role in neuronal function. Furthermore, because internal Ca 2+ release can occur without VGCC activation, particularly after priming (see Fig.…”

Section: Discussionmentioning

confidence: 97%

Metabotropic glutamate receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca²⁺ wave‐dependent activation of SK and TRPC channels

El-Hassar¹,

Hagenston²,

D’Angelo³

et al. 2011

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Non-technical summary The hippocampus is a neural structure that is critical for some forms of memory function. It performs this function through the ability of its neurons to fire patterns of activity that encode information and the ability of the synaptic connections between neurons to strengthen or weaken. Glutamate, an important synaptic neurotransmitter, can activate different types of receptors, including metabotropic glutamate receptors (mGluRs). mGluRs have been shown to be important for learning and memory. It has also been shown that changes in mGluR type 5 might contribute to mental retardation and autism, suggesting that manipulation of mGluR5 might reduce their symptoms. In this study we examined how mGluR activation can activate neuron membrane channels (SK and TRPC) in hippocampal neurons that regulate their activity. Our findings suggest that mGluR activation of SK and TRPC channels are likely to be important for sculpting patterns of activity that encode information by the hippocampus.Abstract Group I metabotropic glutamate receptors (mGluRs) play an essential role in cognitive function. Their activation results in a wide array of cellular and molecular responses that are mediated by multiple signalling cascades. In this study, we focused on Group I mGluR activation of IP 3 R-mediated intracellular Ca 2+ waves and their role in activating Ca 2+ -dependent ion channels in CA1 pyramidal neurons. Using whole-cell patch-clamp recordings and high-speed Ca 2+ fluorescence imaging in acute hippocampal brain slices, we show that synaptic and pharmacological stimulation of mGluRs triggers intracellular Ca 2+ waves and a biphasic electrical response composed of a transient Ca 2+ -dependent SK channel-mediated hyperpolarization and a TRPC-mediated sustained depolarization. The generation and magnitude of the SK channel-mediated hyperpolarization depended solely on the rise in intracellular Ca 2+ concentration ([Ca 2+ ] i ), whereas the TRPC channel-mediated depolarization required both a small rise in [Ca 2+ ] i and mGluR activation. Furthermore, the TRPC-mediated current was suppressed by forskolin-induced rises in cAMP. We also show that SK-and TRPC-mediated currents robustly modulate pyramidal neuron excitability by decreasing and increasing their firing frequency, respectively. These findings provide additional evidence that mGluR-mediated synaptic transmission makes an important contribution to regulating the output of hippocampal neurons through intracellular Ca 2+ wave activation of SK and TRPC channels. cAMP provides an additional level of regulation by modulating TRPC-mediated sustained depolarization that we propose to be important for stabilizing periods of sustained firing.

show abstract

Section: Discussionmentioning

confidence: 97%

Metabotropic glutamate receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca²⁺ wave‐dependent activation of SK and TRPC channels

El-Hassar¹,

Hagenston²,

D’Angelo³

et al. 2011

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…We and others have shown that activation of Isk and Itrpc by Group 1 mGluRs can potently regulate the firing of cortical and hippocampal pyramidal neurons (15, 17, 42) Glutamatergic activation of G q -coupled Group 1 mGluRs triggers the IP 3 signaling pathway and consequent activation of intracellular Ca 2+ waves. Ca 2+ wave propagation to the proximal apical dendrite/soma activates SK channels and a hyperpolarization time-locked to the rise in [Ca 2+ ] i .…”

Section: Discussionmentioning

confidence: 98%

Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels

El-Hassar¹,

Simen²,

Duque³

et al. 2014

Biological Psychiatry

Self Cite

View full text Add to dashboard Cite

Background Disrupted in Schizophrenia 1 (DISC1) is a protein implicated in schizophrenia, bipolar disorder, major depressive disorder, and autism. To date, most of research examining DISC1 function has focused on its role in neurodevelopment, despite its presence throughout life. DISC1 also regulate cAMP signaling by increasing PDE4 catabolism of cAMP when cAMP concentrations are high. In this study, we tested the hypothesis that DISC1, through its regulation of cAMP, modulates I-SK and I-TRPC channel-mediated ionic currents that we have shown previously to regulate the activity of mature prefrontal cortical pyramidal neurons. Methods We used patch-clamp recordings in prefrontal cortical slices from adult rats in which DISC1 function was reduced in vivo by shRNA viral knockdown or in vitro by dialysis of DISC1 antibodies. Results We found that DISC1 disruption resulted in an increase of: mGluR-induced intracellular Ca2+ waves, SK-mediated hyperpolarization and a decrease of TRPC-mediated sustained depolarization. Consistent with a role for DISC1 in regulation of cAMP signaling, forskolin-induced cAMP production also increased intracellular Ca2+ waves, I-SK and decreased I-TRPC. Lastly, inhibiting cAMP generation with guanfacine, an α2A-noradrenergic agonist, normalized the function of SK and TRPC channels. Conclusions Based on our findings, we propose that diminished DISC1 function, such as occurs in some mental disorders, can lead to the disruption of normal patterns of PFC activity through the loss of cAMP regulation of mGluR-mediated intracellular Ca2+ waves, SK and TRPC channel activity.

show abstract

“…an important transcription factor present in the nucleus (Yeckel et al, 2008). In addition to their eccentric location, principal cell nuclei are also infolded in morphology based on qualitative assessments (Holcomb, unpublished data).…”

Section: Functional Consequences Of Nuclear Eccentricitymentioning

confidence: 99%

Polarity and Competition in the Development of the Calyx of Held Terminal in the Medial Nucleus of the Trapezoid Body in the Mouse

Holcomb¹

View full text Add to dashboard Cite

In the auditory brainstem, the connection between globular bushy cells of the anteroventral cochlear nucleus and principal cells (PCs) of the medial nucleus of the trapezoid body (MNTB) is created by one of the largest nerve terminals in the central nervous system, the calyx of Held (CH). The characteristics of the CH:MNTB connection-a short developmental period (48-72 hours), accessibility for recording from pre-and postsynaptic components, and clear monoinnervated end point-make this system an ideal model system for studying nervous system development. Model systems undergo stereotyped stages of development, including exuberant overinnervation, competition between terminals, and a refinement of innervation through removal of weak inputs. However, unlike other similar model systems (climbing fiber:Purkinje cell, retinal ganglion cells:dorsolateral geniculate nucleus), it has been a longstanding question whether the CH:MNTB system undergoes competition. We investigated the innervation state of PCs using the novel technique of segmentation and 3D reconstruction of PCs and their associated inputs across important developmental timepoints (postnatal days (P)2,3,4,6,9,30). This was accomplished by application of serial block-face scanning electron microscopy (SBEM), a method of serial section electron microscopy providing high spatial resolution (~4-10nm) and a high degree of alignment between images with very little section loss. Applying this technique, we show early exuberant innervation of PCs (P2), establish that competition is a common process, and pinpoint the 24-hour period from P3-P4 as a uniquely active day in CH growth during which terminal contact with PCs increases at a rate exceeding 200 µm 2 /day. Common morphological characteristics of the CH:MNTB connection also became qualitatively evident based on 3D reconstructions, particularly an eccentric PC nucleus and preference for polarized terminal growth. Based on these observations, we undertook a quantitative study of polarity in CH:MNTB development using our 3D reconstructions. The results of this investigation demonstrate a novel polarity in development of both the CH and PC; developing PCs are characterized by eccentrically placed nuclei that establish an "intrasomatic polarity" that persists through young adulthood (P30). This polarity appears to define a unique territory opposite of the nuclear location that is amenable to growth of the calyx, is enriched in dendrites, and is selectively enlarged as the principal cell matures to create glia-free surface area for innervation. To our knowledge, this is the first report of a polarity program in the coordinated pre-and postsynaptic development of a non-laminar brain region. Additionally, our findings have codified a progression of dendritic pruning in the maturation of principal cells that may influence and be influenced by the developmental state of the cell. Taken in totality, these results indicate a highly polarized, systemic competitive process in the MNTB during the development of the calyx of He...

show abstract

Intracellular Calcium Waves Transmit Synaptic Information to the Nucleus in Hippocampal Pyramidal Neurons

Cited by 3 publications

References 83 publications

Metabotropic glutamate receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca²⁺ wave‐dependent activation of SK and TRPC channels

Metabotropic glutamate receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca²⁺ wave‐dependent activation of SK and TRPC channels

Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels

Polarity and Competition in the Development of the Calyx of Held Terminal in the Medial Nucleus of the Trapezoid Body in the Mouse

Contact Info

Product

Resources

About

Intracellular Calcium Waves Transmit Synaptic Information to the Nucleus in Hippocampal Pyramidal Neurons

Cited by 3 publications

References 83 publications

Metabotropic glutamate receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca2+ wave‐dependent activation of SK and TRPC channels

Metabotropic glutamate receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca2+ wave‐dependent activation of SK and TRPC channels

Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels

Polarity and Competition in the Development of the Calyx of Held Terminal in the Medial Nucleus of the Trapezoid Body in the Mouse

Contact Info

Product

Resources

About

Metabotropic glutamate receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca²⁺ wave‐dependent activation of SK and TRPC channels

Metabotropic glutamate receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca²⁺ wave‐dependent activation of SK and TRPC channels