Kinetics and activation of postsynaptic kainate receptors at thalamocortical synapses: role of glutamate clearance.

نویسندگان

  • F L Kidd
  • J T Isaac
چکیده

Kainate (KA) receptor-mediated excitatory postsynaptic currents (EPSCs) exhibit slow kinetics at the great majority of synapses. However, native or heterologously expressed KA receptors exhibit rapid kinetics in response to agonist application. One possibility to explain this discrepancy is that KA receptors are extrasynaptic and sense glutamate diffusing from the synaptic cleft. We investigated this by studying the effect of three manipulations that change glutamate clearance on evoked KA EPSCs at thalamocortical synapses. First, we used high-frequency stimulation to increase extrasynaptic glutamate levels. This caused an apparent increase in the relative contribution of the KA EPSC to transmission and slowed the decay kinetics. However, scaling and summing the EPSC evoked at low frequency reproduced this, demonstrating that the effect was due to postsynaptic summation of KA EPSCs. Second, we applied inhibitors of high-affinity glutamate transport. This caused a depression in both AMPA and KA EPSC amplitude due to the activation of a presynaptic glutamatergic autoreceptor. However, transport inhibitors had no selective effect on the amplitude or kinetics of the KA EPSC. Third, to increase glutamate clearance, we raised temperature during recordings. This shortened the decay of both the AMPA and KA components and increased their amplitudes, but this effect was the same for both. Therefore these data provide evidence against glutamate diffusion out of the synaptic cleft as the mechanism for the slow kinetics of KA EPSCs. Other possibilities such as interactions of KA receptors with other proteins or novel properties of native synaptic heteromeric receptors are required to explain the slow kinetics.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

(S)- 3,5-Dihydroxyphenylglycine )an agonist for group I metabotropic glutamate receptors( induced synaptic potentiation at excitatory synapses on fast spiking GABAergic cells in visual cortex

Introduction: (S)- 3,5-Dihydroxyphenylglycine (DHPG) is an agonist for group I metabotropic glutamate receptors. DHPG-induced synaptic depression of excitatory synapses on hippocampal pyramidal neurons is well known model for synaptic plasticity studies. The aim of the present study was to examine the effects of DHPG superfusion on excitatory synapses on pyramidal and fast-spiking GABAergic cel...

متن کامل

Auditory thalamocortical synaptic transmission in vitro.

To facilitate an understanding of auditory thalamocortical mechanisms, we have developed a mouse brain-slice preparation with a functional connection between the ventral division of the medial geniculate (MGv) and the primary auditory cortex (ACx). Here we present the basic characteristics of the slice in terms of physiology (intracellular and extracellular recordings, including current source ...

متن کامل

Role of presynaptic kainate receptors at parallel fiber-purkinje cell synapses in induction of cerebellar LTD: interplay with climbing fiber input.

Until recently, except for A1 adenosine, N-methyl-d-aspartate, and cannabinoid receptors, little effort has been made to unravel possible roles of parallel fiber (PF) presynaptic receptors in long-term depression (LTD) of synaptic transmission at PF-Purkinje cell (PC) synapses. Presynaptic kainate (KA) receptors are also present on PFs and might also influence LTD induction by modulating glutam...

متن کامل

Synaptic Activation of Presynaptic Kainate Receptors on Hippocampal Mossy Fiber Synapses

Kainate receptors (KARs) are a poorly understood family of ionotropic glutamate receptors. A role for these receptors in the presynaptic control of transmitter release has been proposed but remains controversial. Here, KAR agonists are shown to enhance fiber excitability, and a number of experiments show that this is a direct effect of KARs on the presynaptic fibers. In addition, KAR activation...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of neurophysiology

دوره 86 3  شماره 

صفحات  -

تاریخ انتشار 2001