POLYAMINES FACILITATE SYNAPTIC RESPONSES MEDIATED BY GluR2-DEFICIENT AMPA RECEPTORS IN IMMATURE LAYER V PYRAMIDAL NEURONS
Abstract number :
1.051
Submission category :
Year :
2003
Submission ID :
3927
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Jieun Shin, John R. Huguenard Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA
AMPA receptors mediate the majority of fast excitation in the CNS and play key roles in generalization of seizure activity. The presence or absence of GluR2 in synaptic AMPA receptors will influence post-synaptic mechanisms such as Ca permeability and short-term plasticity. Receptors lacking GluR2 should have enhanced paired-pulse facilitation due to polyamine-dependent unblocking (Rozov and Burnashev, 1999 [italic]Nature[/italic] 40:594-598). We tested whether such unblocking occurs in immature neocortical pyramidal cells, which have recently been shown to express relatively low levels of functional GluR2 at synapses (Kumar et al, 2002 [italic]J Neurosci[/italic] 22:3005-3015).
Whole cell recordings were used to obtain synaptic responses in layer V pyramidal neurons of P12-14 or P16-18 rats and spermine (50mM) was either included or excluded from the pipette solution. We recorded the responses to paired (50Hz) stimuli and measured the rectification index (RI) and paired-pulse ratio (PPR) at the two developmental stages.
At the immature stage ([lt]P15) inclusion of intracellular spermine increased both RI (from 0.54 [plusmn] 0.04, to 0.36 [plusmn] 0.04, n=7, p[lt]0.01) and PPR (from 1.21 to 1.68 n=7, p[lt]0.05), but had little or no effect on RI (1.13 [plusmn] 0.47 to 1.13 [plusmn] 0.35, n=6, N.S.) or PPR (1.09 [plusmn] 0.14 to 1.01 [plusmn] 0.32, n=5, N.S.) in more mature (P16-18) pyramidal neurons.
These results provide further support for the idea that excitatory synapses on immature neocortical pyramidal neurons contain AMPA receptors lacking the GluR2 subunit. Three properties expected for GluR2-deficient receptors were found in immature neurons: 1) a low RI indicating strong inward rectification, 2) an increase in RI upon addition of spermine, and 3) and an increase in PPR produced by spermine. As a consequence of GluR2 deficiency, a post-synaptic component of synaptic facilitation occurs during paired stimuli, which depends on the level of intracellular spermine. These results have important implications regarding repetitive activation of neocortical circuits both in the normal state and during seizures.
[Supported by: NINDS.]