Synaptic plasticity by antidromic firing during hippocampal network oscillations

Abstract

Learning and other cognitive tasks require integrating new experiences into context. In contrast to sensory-evoked synaptic plasticity, comparatively little is known of how synaptic plasticity may be regulated by intrinsic activity in the brain, much of which can involve nonclassical modes of neuronal firing and integration. Coherent high-frequency oscillations of electrical activity in CA1 hippocampal neurons [sharp-wave ripple complexes (SPW-Rs)] functionally couple neurons into transient ensembles. These oscillations occur during slow-wave sleep or at rest. Neurons that participate in SPW-Rs are distinguished from adjacent nonparticipating neurons by firing action potentials that are initiated ectopically in the distal region of axons and propagate antidromically to the cell body. This activity is facilitated by GABA A -mediated depolarization of axons and electrotonic coupling. The possible effects of antidromic firing on synaptic strength are unknown. We find that facilitation of spontaneous SPW-Rs in hippocampal slices by increasing gap-junction coupling or by GABA A -mediated axon depolarization resulted in a reduction of synaptic strength, and electrical stimulation of axons evoked a widespread, long-lasting synaptic depression. Unlike other forms of synaptic plasticity, this synaptic depression is not dependent upon synaptic input or glutamate receptor activation, but rather requires L-type calcium channel activation and functional gap junctions. Synaptic stimulation delivered after antidromic firing, which was otherwise too weak to induce synaptic potentiation, triggered a long-lasting increase in synaptic strength. Rescaling synaptic weights in subsets of neurons firing antidromically during SPW-Rs might contribute to memory consolidation by sharpening specificity of subsequent synaptic input and promoting incorporation of novel information.long-term depression | long-term potentiation | network plasticity | excitability M emory requires more than recording sensory input (1-3).New sensory experience must be incorporated into a cognitive framework, or schema, that preserves temporal sequence and associates the new information together with other relevant aspects of the experience (4). This central processing requires coupling neurons into transiently stable functional assemblies and transferring information between different brain regions (2, 5). The functional coupling of neurons within assemblies is believed to be organized by network oscillations that cover multiple frequency bands and follow distinct mechanisms (6). During slow-wave sleep (SWS) and quiet wakefulness, characterized by decreased sensory and cognitive processing, hippocampal neurons fire in brief periods of high-frequency coherent oscillations (100-300 Hz), termed sharp-wave ripple complexes (SPW-Rs). SPW-Rs coincide with periods of offline replay of neural sequences learned during encoding sensory information (7,8). Disrupting SPW-Rs, and therefore replay, impairs memory retention (9, 10), suggesting that replay of activity sequences...

Regulation of Hippocampal Firing by Network Oscillations during Sleep

“…Another possibility is that recurrent conduction delays combined with synchronous population bursts during SWRs produce depression at CA3 synapses [38] (but see [39]). A third possible scenario is that the biophysical mechanisms underlying SWRs serve to downscale synaptic connections, either through dendritic depolarization in the absence of postsynaptic spiking [12, 13, 40], or through the antidromic propagation of spikes [41]. Similarly, during spindles, Ca 2+ influx coupled with shunted somatic spiking [14, 23] and an 8-16 Hz timescale [42, 43] are fully consistent with LTD.…”

Mechanisms of heterosynaptic metaplasticity

“…B 369: 20130148 subsequent synaptic plasticity in a BCM-like manner [9,11]. However, under other conditions, cell firing is neither necessary nor sufficient for BCM-like heterosynaptic metaplasticity [8,12]. In fact, cell firing in these cases facilitated rather than inhibited subsequent LTP.…”

BDNF mRNA abundance regulated by antidromic action potentials and AP-LTD in hippocampus

“…Antidromic action potential firing in these neurons in the absence of excitatory synaptic input induces a form of synaptic plasticity that reduces the strength of synapses in a cell-wide manner, termed action potential-induced long-term depression (AP-LTD) [3]. Mechanisms known to promote antidromic firing during SPWRs facilitate AP-LTD induction [3]. Although AP-LTD has not yet been studied in vivo, the phenomenon appears relevant to memory consolidation because SPW-Rs occur during slow-wave sleep (SWS) and quiet periods of wakefulness.…”