Disinhibition-Mediated LTP in the Hippocampus is Synapse Specific

Paired pre- and postsynaptic activity in area CA1 of the hippocampus induces long-term inhibitory synaptic plasticity at GABAergic synapses. This pairing-induced GABAergic plasticity weakens synaptic inhibition due to a depolarization of the reversal potential for GABAA receptor-mediated currents (EGABA) through a decrease in the function of the neuron-specific K+–Cl− cotransporter KCC2. When pairing-induced GABAergic plasticity is induced at feed-forward inhibitory synapses in the CA1, the decrease in inhibition produces an increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials in pyramidal neurons. This form of inhibitory synaptic plasticity is termed disinhibition-mediated long-term potentiation (LTP). In the present study, we investigated whether disinhibition-mediated LTP is synapse specific. We performed these experiments in hippocampal slices prepared from adult Sprague Dawley rats. We found that the underlying depolarization of EGABA is not restricted to the paired pathway, but rather is expressed to the same extent at unpaired control pathways. However, the overall strength of GABAergic transmission is maintained at the unpaired pathway by a heterosynaptic increase in GABAergic conductance. The pairing-induced depolarization of EGABA at the paired and unpaired pathways required Ca2+-influx through both the L-type voltage-gated Ca2+ channels and N-methyl-d-aspartic acid receptors. However, only Ca2+-influx through L-type channels was required for the increased conductance at the unpaired pathway. As a result of this increased GABAergic conductance, disinhibition-mediated LTP remains confined to the paired pathway and thus is synapse specific, suggesting it may be a novel mechanism for hippocampal-dependent learning and memory

GABAergic Synaptic Transmission Regulates Calcium Influx During Spike-Timing Dependent Plasticity

Coincident pre- and postsynaptic activity of hippocampal neurons alters the strength of gamma-aminobutyric acid (GABAA)-mediated inhibition through a Ca2+-dependent regulation of cation-chloride cotransporters. This long-term synaptic modulation is termed GABAergic spike-timing dependent plasticity (STDP). In the present study, we examined whether the properties of the GABAergic synapses themselves modulate the required postsynaptic Ca2+ influx during GABAergic STDP induction. To do this we first identified GABAergic synapses between cultured hippocampal neurons based on their relatively long decay time constants and their reversal potentials which lay close to the resting membrane potential. GABAergic STDP was then induced by coincidentally (±1 ms) firing the pre- and postsynaptic neurons at 5 Hz for 30 s, while postsynaptic Ca2+ was imaged with the Ca2+-sensitive fluorescent dye Fluo4-AM. In all cases, the induction of GABAergic STDP increased postsynaptic Ca2+ above resting levels. We further found that the magnitude of this increase correlated with the amplitude and polarity of the GABAergic postsynaptic current (GPSC); hyperpolarizing GPSCs reduced the Ca2+ influx in comparison to both depolarizing GPSCs, and postsynaptic neurons spiked alone. This relationship was influenced by both the driving force for Cl− and GABAA conductance (which had positive correlations with the Ca2+ influx). The spike-timing order during STDP induction did not influence the correlation between GPSC amplitude and Ca2+ influx, which is likely accounted for by the symmetrical GABAergic STDP window

Spike-Timing Dependent Plasticity in Inhibitory Circuits

Inhibitory circuits in the brain rely on GABA-releasing interneurons. For long, inhibitory circuits were considered weakly plastic in the face of patterns of neuronal activity that trigger long-term changes in the synapses between excitatory principal cells. Recent studies however have shown that GABAergic circuits undergo various forms of long-term plasticity. For the purpose of this review, we identify three major long-term plasticity expression sites. The first locus is the glutamatergic synapses that excite GABAergic inhibitory cells and drive their activity. Such synapses, on many but not all inhibitory interneurons, exhibit long-term potentiation (LTP) and depression (LTD). Second, GABAergic synapses themselves can undergo changes in GABA release probability or postsynaptic GABA receptors. The third site of plasticity is in the postsynaptic anion gradient of GABAergic synapses; coincident firing of GABAergic axons and postsynaptic neurons can cause a long-lasting change in the reversal potential of GABAA receptors mediating fast inhibitory postsynaptic potentials. We review the recent literature on these forms of plasticity by asking how they may be triggered by specific patterns of pre- and postsynaptic action potentials, although very few studies have directly examined spike-timing dependent plasticity (STDP) protocols in inhibitory circuits. Plasticity of interneuron recruitment and of GABAergic signaling provides for a rich flexibility in inhibition that may be central to many aspects of brain function. We do not consider plasticity at glutamatergic synapses on Purkinje cells and other GABAergic principal cells

Kainate Receptors Coexist in a Functional Complex with KCC2 and Regulate Chloride Homeostasis in Hippocampal Neurons

Peer reviewe

Disinhibition Mediates a Form of Hippocampal Long-Term Potentiation in Area CA1

The hippocampus plays a central role in memory formation in the mammalian brain. Its ability to encode information is thought to depend on the plasticity of synaptic connections between neurons. In the pyramidal neurons constituting the primary hippocampal output to the cortex, located in area CA1, firing of presynaptic CA3 pyramidal neurons produces monosynaptic excitatory postsynaptic potentials (EPSPs) followed rapidly by feedforward (disynaptic) inhibitory postsynaptic potentials (IPSPs). Long-term potentiation (LTP) of the monosynaptic glutamatergic inputs has become the leading model of synaptic plasticity, in part due to its dependence on NMDA receptors (NMDARs), required for spatial and temporal learning in intact animals. Using whole-cell recording in hippocampal slices from adult rats, we find that the efficacy of synaptic transmission from CA3 to CA1 can be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, we show that the induction of GABAergic plasticity at feedforward inhibitory inputs results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials. Like classic LTP, disinhibition-mediated LTP requires NMDAR activation, suggesting a role in types of learning and memory attributed primarily to the former and raising the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain

Xバンド電子スピン共鳴によるGaAs;Er,OのEr濃度およびキャリア依存性の研究

博士（理学）神戸大

The role of trophic factors in synapse formation and plasticity between identified Lymnaea neurons

Bibliography: p. 198-231

Circadian organization of diving behaviour and respiratory chemoreflexes in birds

grantor: University of TorontoThe circadian rhythm in diving behaviour of captive canvasback ducks Aythya valisineria was measured using radio-telemetry, and indirectly via analysis of underwater feeding activity. The asphyxic ventilatory response then was measured in awake unanesthetized ducks by closed-circuit plethysmography at the times corresponding to maximum and minimum dive activity. 76% of dives occurred at night and nocturnal dives were 37% longer than those performed in the light. The day-night differences in diving behaviour were apparently correlated with day-night differences in respiratory chemosensitivity. The ventilatory response to progressive asphyxia was non-linear, and consisted of an increase in tidal volume with no change in respiratory frequency. Respiratory sensitivity to asphyxia, as reflected by the exponential regression coefficient (the slope of lnV\sb{\rm I} versus (CO\sb2)), was lower at night than during the day (P = 0.02). I suggest that underwater exercise performance is facilitated by reduced respiratory chemosensitivity and that the respiratory and behavioural control systems are synchronized by the circadian timing system.M.Sc

Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the Hippocampus

Disinhibition-mediated long-term potentiation (LTP) in the CA1 region of the hippocampus involves GABAergic synaptic plasticity at feedforward inhibitory inputs, resulting in the reduced shunting of glutamatergic excitatory currents. The GABAergic plasticity which underlies disinhibition-mediated LTP results from a Ca2+-dependent decrease in the activity of the K+-Cl- cotransporter (KCC2), depolarizing the reversal potential for GABAA receptor-mediated currents (EGABA), thereby attenuating inhibition. Muscarinic acetylcholine receptor (mAChR) activation has previously been shown to regulate classic glutamatergic LTP, modulate intracellular [Ca2+] and signaling, and facilitate the excitability of GABAergic interneurons in the CA1. Based on these effects, and the ability of mAChR activation to regulate CA1 pyramidal neuron KCC2 expression, we proposed that mAChR activation would modulate disinhibition-mediated LTP. To test this prediction, we made whole cell recordings from CA1 pyramidal neurons in hippocampal slices. Disinhibition-mediated LTP was induced using a spike timing-dependent plasticity (STDP) protocol, which involved coincident presynaptic stimulation and postsynaptic current injection (at 5 Hz for 60 seconds). We found that mAChR activation via carbachol (CCh) prevented the induction of disinhibition-mediated LTP. Moreover, in the presence of CCh, EGABA failed to depolarize following plasticity induction. Lastly, we recorded the paired-pulse ratio (PPR) during the induction of disinhibition-mediated LTP and found that in the presence of CCh, plasticity induction induced a significant paired-pulse depression. This suggests that presynaptic mAChR activation may prevent the postsynaptic expression of disinhibition-mediated LTP