Noradrenergic Regulation of Synaptic Plasticity in the Hippocampal CA1 Region

Katsuki, Hiroshi, Yukitoshi Izumi, and Charles F. Zorumski. Noradrenergic regulation of synaptic plasticity in the hippocampal CA1 region. J. Neurophysiol. 77: 3013–3020, 1997. The effects of norepinephrine (NE) and related agents on long-lasting changes in synaptic efficacy induced by several patterns of afferent stimuli were investigated in the CA1 region of rat hippocampal slices. NE (10 μM) showed little effect on the induction of long-term potentiation (LTP) triggered by theta-burst-patterned stimulation, whereas it inhibited the induction of long-term depression (LTD) triggered by 900 pulses of 1-Hz stimulation. In nontreated slices, 900 pulses of stimuli induced LTD when applied at lower frequencies (1–3 Hz), and induced LTP when applied at a higher frequency (30 Hz). NE (10 μM) caused a shift of the frequency-response relationship in the direction preferring potentiation. The effect of NE was most prominent at a stimulus frequency of 10 Hz, which induced no changes in control slices but clearly induced LTP in the presence of NE. The facilitating effect of NE on the induction of LTP by 10-Hz stimulation was blocked by theβ-adrenergic receptor antagonist timolol (50 μM), but not by the α receptor antagonist phentolamine (50 μM), and was mimicked by the β-agonist isoproterenol (0.3 μM), but not by the α1 agonist phenylephrine (10 μM). The induction of LTD by 1-Hz stimulation was prevented by isoproterenol but not by phenylephrine, indicating that the activation of β-receptors is responsible for these effects of NE. NE (10 μM) also prevented the reversal of LTP (depotentiation) by 900 pulses of 1-Hz stimulation delivered 30 min after LTP induction. In contrast to effects on naive (nonpotentiated) synapses, the effect of NE on previously potentiated synapses was only partially mimicked by isoproterenol, but fully mimicked by coapplication of phenylephrine and isoproterenol. In addition, the effect of NE was attenuated either by phentolamine or by timolol, indicating that activation of both α1 and β-receptors is required. These results show that NE plays a modulatory role in the induction of hippocampal synaptic plasticity. Althoughβ-receptor activation is essential, α1 receptor activation is also necessary in determining effects on previously potentiated synapses.

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Long-Term Potentiation in the Hippocampal CA1 Region Does Not Require Insertion and Activation of GluR2-Lacking AMPA Receptors

Journal of Neurophysiology ◽

10.1152/jn.00473.2007 ◽

2007 ◽

Vol 98 (4) ◽

pp. 2488-2492 ◽

Cited By ~ 56

Author(s):

Erin E. Gray ◽

Ann E. Fink ◽

Joshua Sariñana ◽

Bryce Vissel ◽

Thomas J. O'Dell

Keyword(s):

Glutamate Receptor ◽

Ampa Receptors ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Old Mice

Activity-dependent insertion of AMPA-type glutamate receptors is thought to underlie long-term potentiation (LTP) at Schaffer collateral fiber synapses on pyramidal cells in the hippocampal CA1 region. Although it is widely accepted that the AMPA receptors at these synapses contain glutamate receptor type 2 (GluR2) subunits, recent findings suggest that LTP in hippocampal slices obtained from 2- to 3-wk-old rodents is dependent on the transient postsynaptic insertion and activation of Ca2+-permeable, GluR2-lacking AMPA receptors. Here we examined whether LTP in slices prepared from adult animals exhibits similar properties. In contrast to previously reported findings, pausing synaptic stimulation for as long as 30 min post LTP induction had no effect on LTP maintenance in slices from 2- to 3-mo-old mice. LTP was also not disrupted by postinduction application of a selective blocker of GluR2-lacking AMPA receptors or the broad-spectrum glutamate receptor antagonist kynurenate. Although these results suggest that the role of GluR2-lacking AMPA receptors in LTP might be regulated during postnatal development, LTP in slices obtained from 15- to 21-day-old mice also did not require postinduction synaptic stimulation or activation of GluR2-lacking AMPA receptors. Thus the insertion and activation of GluR2-lacking AMPA receptors do not appear to be fundamental processes involved in LTP at excitatory synapses in the hippocampal CA1 region.

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Phosphatidylinositol 3-Kinase Is Required for the Expression But Not for the Induction or the Maintenance of Long-Term Potentiation in the Hippocampal CA1 Region

Journal of Neuroscience ◽

10.1523/jneurosci.22-09-03359.2002 ◽

2002 ◽

Vol 22 (9) ◽

pp. 3359-3365 ◽

Cited By ~ 157

Author(s):

Pietro Paolo Sanna ◽

Maurizio Cammalleri ◽

Fulvia Berton ◽

Cindy Simpson ◽

Robert Lutjens ◽

...

Keyword(s):

Long Term Potentiation ◽

Phosphatidylinositol 3 Kinase ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Phosphatidylinositol 3

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AMPA Silencing Is a Prerequisite for Developmental Long-Term Potentiation in the Hippocampal CA1 Region

Journal of Neurophysiology ◽

10.1152/jn.90476.2008 ◽

2008 ◽

Vol 100 (5) ◽

pp. 2605-2614 ◽

Cited By ~ 23

Author(s):

Therése Abrahamsson ◽

Bengt Gustafsson ◽

Eric Hanse

Keyword(s):

Developmental Stages ◽

Long Term Potentiation ◽

Synaptic Strength ◽

Ca1 Region ◽

Hippocampal Ca1 Region ◽

Silent Synapses ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Hippocampal Ca3

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) unsilencing is an often proposed expression mechanism both for developmental long-term potentiation (LTP), involved in circuitry refinement during brain development, and for mature LTP, involved in learning and memory. In the hippocampal CA3–CA1 connection naïve (nonstimulated) synapses are AMPA signaling and AMPA-silent synapses are created from naïve AMPA-signaling (AMPA-labile) synapses by test-pulse synaptic activation (AMPA silencing). To investigate to what extent LTPs at different developmental stages are explained by AMPA unsilencing, the amount of LTP obtained at these different developmental stages was related to the amount of AMPA silencing that preceded the induction of LTP. When examined in the second postnatal week Hebbian induction was found to produce no more stable potentiation than that causing a return to the naïve synaptic strength existing prior to the AMPA silencing. Moreover, in the absence of a preceding AMPA silencing Hebbian induction produced no stable potentiation above the naïve synaptic strength. Thus this early, or developmental, LTP is nothing more than an unsilencing (dedepression) and stabilization of the AMPA signaling that was lost by the prior AMPA silencing. This dedepression and stabilization of AMPA signaling was mimicked by the presence of the protein kinase A activator forskolin. As the relative degree of AMPA silencing decreased with development, LTP manifested itself more and more as a “genuine” potentiation (as opposed to a dedepression) not explained by unsilencing and stabilization of AMPA-labile synapses. This “genuine,” or mature, LTP rose from close to nothing of total LTP prior to postnatal day (P)13, to about 70% of total LTP at P16, and to about 90% of total LTP at P30. Developmental LTP, by stabilization of AMPA-labile synapses, thus seems adapted to select synaptic connections to the growing synaptic network. Mature LTP, by instead strengthening existing stable connections between cells, may then create functionally tightly connected cell assemblies within this network.

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