Activity-Dependent Depression of Local Excitatory Connections in the CA1 Region of Mouse Hippocampus

Abstract

Fink AE, Sarinana J, Gray EE, O'Dell TJ. Activity-dependent depression of local excitatory connections in the CA1 region of mouse hippocampus. J Neurophysiol 97: 3926 -3936, 2007. First published April 4, 2007 doi:10.1152/jn.00213.2007. The existence of recurrent excitatory synapses between pyramidal cells in the hippocampal CA1 region has been known for some time yet little is known about activity-dependent forms of plasticity at these synapses. Here we demonstrate that under certain experimental conditions, Schaffer collateral/commissural fiber stimulation can elicit robust polysynaptic excitatory postsynaptic potentials due to recurrent synaptic inputs onto CA1 pyramidal cells. In contrast to CA3 pyramidal cell inputs, recurrent synapses onto CA1 pyramidal cells exhibited robust pairedpulse depression and a sustained, but rapidly reversible, depression in response to low-frequency trains of Schaffer collateral fiber stimulation. Blocking GABA B receptors abolished paired-pulse depression but had little effect on low-frequency stimulation (LFS)-induced depression. Instead, LFS-induced depression was significantly attenuated by an inhibitor of A1 type adenosine receptors. Blocking the postsynaptic effects of GABA B and A1 receptor activation on CA1 pyramidal cell excitability with an inhibitor of G-protein-activated inwardly rectifying potassium channels had no effect on either pairedpulse depression or LFS-induced depression. Thus activation of presynaptic GABA B and adenosine receptors appears to have an important role in activity-dependent depression at recurrent synapses. Together, our results indicate that CA3-CA1 and CA1-CA1 synapses exhibit strikingly different forms of short-term synaptic plasticity and suggest that activity-dependent changes in recurrent synaptic transmission can transform the CA1 region from a sparsely connected recurrent network into a predominantly feedforward circuit.

Synchronization through nonreciprocal connections in a hybrid hippocampus microcircuit

“…The recurrent excitation implemented in “Circuit 5” is common in neocortical microcircuits (Silberberg and Markram, 2007) and, while not as common in CA1, there are a number of studies demonstrating their existence (Crépel et al, 1997; Aniksztejn et al, 2001; Fink et al, 2007). Feedback connections among CA1 PCs are prevalent in the developing brain but are rarely found in the adult hippocampus (Crépel et al, 1997).…”

“…Deuchars and Thomson (1996) reported connections between CA1 PC in about 1% of their recorded pairs. Blocking inhibition, however, increased the likelihood of finding PC to PC connections in CA1 (Crépel et al, 1997; Fink et al, 2007). Lesions using kainate in rats also promote CA1 the appearance of PC connection recurrence (Perez et al, 1996).…”

“…Lesions using kainate in rats also promote CA1 the appearance of PC connection recurrence (Perez et al, 1996). Feedback CA1 PC synapses are also special in terms of synaptic plasticity and activity history can convert CA1 from a parallel circuit to a network with sparse recurrence (Fink et al, 2007). Hence, the connection scenario of “Circuit 5” is plausible in both neocortex and hippocampus (Cobb et al, 1995; Silberberg and Markram, 2007).…”

Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome

“…Successful isolation of GABA B mediated currents was tested through use of 2 μM CGP55845 (a specific GABA B receptor antagonist) which completely inhibited slow IPSCs within 5 minutes of perfusion (n=16). Likewise slow IPSCs were partially suppressed by GIRK channel blockers tertiapin-Q (100 nM, n=5, 55 ± 0.1% at 15 minutes) and SCH23390 (10 μM, n=6, 54 ± 0.1% at 12 minutes) (Fink, et al, 2007, Jelacic, et al, 2000, Kuzhikandathil and Oxford, 2002). Incomplete block of slow IPSCs by GIRK channel blockers may be due to heterogenous GABA B postsynaptic currents, partial block, or use dependence (Best, et al, 2007, Kanjhan, et al, 2005, Pham, et al, 1998, Tabata, et al, 2005).…”

Differentiation of forebrain and hippocampal dopamine 1-class receptors, D1R and D5R, in spatial learning and memory

“…However, D1R/D5R antagonists block norepinephrine and serotonergic receptors (5HT-2), the serotonin transporter, which expresses throughout the hippocampus, and other g-protein coupled receptors. Hicks et al, 1984;Ohlstein and Berkowitz, 1985;Fink et al, 2007;Zarrindast et al, 2011), obscuring a strong conclusion as to whether hippocampal D1R activation is truly required for spatial learning and memory. Our data, shows that the D1R primarily expresses in the DG of the hippocampus, but not CA3 or CA1 (Supporting Information Fig.…”