Information processing in the axon

It is widely accepted that the hippocampus plays a major role in learning and memory. The mossy fiber synapse between granule cells in the dentate gyrus and pyramidal neurons in the CA3 region is a key component of the hippocampal trisynaptic circuit. Recent work, partially based on direct presynaptic patch-clamp recordings from hippocampal mossy fiber boutons, sheds light on the mechanisms of synaptic transmission and plasticity at mossy fiber synapses. A high Na + channel density in mossy fiber boutons leads to a large amplitude of the presynaptic action potential. Together with the fast gating of presynaptic Ca 2+ channels, this generates a large and brief presynaptic Ca 2+ influx, which can trigger transmitter release with high efficiency and temporal precision. The large number of release sites, the large size of the releasable pool of vesicles, and the huge extent of presynaptic plasticity confer unique strength to this synapse, suggesting a large impact onto the CA3 pyramidal cell network under specific behavioral conditions. The characteristic properties of the hippocampal mossy fiber synapse may be important for pattern separation and information storage in the dentate gyrus-CA3 cell network.Keywords Presynaptic recording . Mossy fiber boutons . Mossy fiber synapses . Hippocampus . Autoassociative networks . Episodic memory . Synaptic efficacyThe mossy fiber synapse: a key connection in the hippocampal networkThe hippocampal formation consists of three types of principal neurons: granule cells in the dentate gyrus, CA3 pyramidal cells, and CA1 pyramidal neurons. These cells are interconnected by glutamatergic synapses, forming the classical trisynaptic circuit (Fig. 1a,b). Dentate gyrus granule cells receive excitatory glutamatergic input from layer 2 pyramidal cells of the entorhinal cortex and project to CA3 pyramidal cells. CA3 pyramidal cells project to CA1 cells, which in turn project to the subiculum and back to the entorhinal cortex [4]. In addition to this trisynaptic circuit, there is also a direct input from the entorhinal cortex to both CA3 and CA1 pyramidal cells. Furthermore, CA3 pyramidal neurons are extensively connected to each other via recurrent collateral synapses.The nonmyelinated axons of the granule cells, the socalled mossy fibers, show several structural properties that distinguish them from the other synaptic pathways [39]. They project to the CA3 region, mainly traveling within a narrow band termed "stratum lucidum." Several (∼15) large "giant" boutons (∼3-5-μm diameter) emerge from a single mossy fiber axon, either arranged in an en passant manner or attached to the main axon via a short perpendicular axonal branch [1,8,29,31] (Fig. 1c,d). A large mossy fiber bouton typically contacts only a single CA3 pyramidal neuron [21], and a mossy fiber axon contacts a given CA3 pyramidal neuron only once, as boutons are ∼150 μm apart. As the rat hippocampus contains ∼1 million granule cells

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“…Are hippocampal mossy fibers involved in information processing [23]? Or do they follow the rule, "The axon does not think.…”

Section: Abstract Presynaptic Recording Mossy Fiber Boutons Mossymentioning

confidence: 99%

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Bischofberger

Engel

Frotscher

et al. 2006

Pflugers Arch - Eur J Physiol

114

110

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“…channels by presynaptic voltage waveforms Several recent studies suggest that signaling in mossy fiber axons and MFBs is highly complex (for review, see Bischofberger et al, 2006a) (see also Debanne, 2004). First, the duration of the presynaptic action potential is not constant, but shows broadening during repetitive stimulation (Geiger and Jonas, 2000).…”

Section: Differential Recruitment Of Camentioning

confidence: 99%

Differential Gating and Recruitment of P/Q-, N-, and R-Type Ca²⁺Channels in Hippocampal Mossy Fiber Boutons

Li¹,

Bischofberger²,

Jónás³

2007

J. Neurosci.

185

199

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Voltage-gated Ca 2ϩ channels in presynaptic terminals initiate the Ca 2ϩ inflow necessary for transmitter release. At a variety of synapses, multiple Ca 2ϩ channel subtypes are involved in synaptic transmission and plasticity. However, it is unknown whether presynaptic Ca 2ϩ channels differ in gating properties and whether they are differentially activated by action potentials or subthreshold voltage signals. We examined Ca 2ϩ channels in hippocampal mossy fiber boutons (MFBs) by presynaptic recording, using the selective blockers -agatoxin IVa, -conotoxin GVIa, and SNX-482 to separate P/Q-, N-, and R-type components. Nonstationary fluctuation analysis combined with blocker application revealed a single MFB contained on average ϳ2000 channels, with 66% P/Q-, 26% N-, and 8% R-type channels. Whereas both P/Q-type and N-type Ca 2ϩ channels showed high activation threshold and rapid activation and deactivation, R-type Ca 2ϩ channels had a lower activation threshold and slower gating kinetics. To determine the efficacy of activation of different Ca 2ϩ channel subtypes by physiologically relevant voltage waveforms, a six-state gating model reproducing the experimental observations was developed. Action potentials activated P/Q-type Ca 2ϩ channels with high efficacy, whereas N-and R-type channels were activated less efficiently. Action potential broadening selectively recruited N-and R-type channels, leading to an equalization of the efficacy of channel activation. In contrast, subthreshold presynaptic events activated R-type channels more efficiently than P/Q-or N-type channels. In conclusion, single MFBs coexpress multiple types of Ca 2ϩ channels, which are activated differentially by subthreshold and suprathreshold presynaptic voltage signals.

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“…5. These criteria have been used before to distinguish different axonal morphologies (Debanne, 2004;Kriegsfeld et al, 2004). We adapted these classifications and defined fibers of passage as fibers carrying sparse, scattered varicosities and no arborizations or ramifications (Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification of central projections from amylin-activated neurons to the lateral hypothalamus

2010

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The ability of the pancreatic hormone amylin to inhibit food intake relies on a direct activation of the area postrema (AP). This activation is synaptically transmitted to the nucleus of the solitary tract (NTS), the lateral parabrachial nucleus (LPB), the central amygdaloid nucleus (Ce) and the lateral bed nucleus of stria terminalis (BSTL). Interestingly, neurons of the rostro-dorsal lateral hypothalamic area (dLHA), which are activated during fasting, are inhibited by peripheral amylin, although they lack amylin receptors. Using the retrograde tracer cholera toxin-B (Ctb) we analyzed whether the dLHA receives neuronal projections from amylin-activated brain areas. The anterograde tracer biotinylated dextran-amine (BDA) was used to confirm the projections and to identify further neuronal pathways potentially involved in amylin signaling. We identified dense projections from the amylin activated neurons in the LPB and sparse projections from the NTS to the dLHA. LPB fiber efferents were found in close proximity to dLHA nuclei activated by 24h of fasting. The AP and the Ce showed no projections to the dLHA. Dense efferents were also observed from the LPB to other hypothalamic areas, namely to the ventromedial, dorsomedial, paraventricular and arcuate nuclei. This study provides neuroanatomical evidence that among the amylin activated areas, the LPB provides the strongest input to the dLHA, thus it may mediate the amylin-induced inhibition of the dLHA. ABSTRACTThe ability of the pancreatic hormone amylin to inhibit food intake relies on a direct

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Information processing in the axon

Cited by 356 publications

References 143 publications

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Differential Gating and Recruitment of P/Q-, N-, and R-Type Ca²⁺Channels in Hippocampal Mossy Fiber Boutons

Identification of central projections from amylin-activated neurons to the lateral hypothalamus

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Information processing in the axon

Cited by 356 publications

References 143 publications

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Differential Gating and Recruitment of P/Q-, N-, and R-Type Ca2+Channels in Hippocampal Mossy Fiber Boutons

Identification of central projections from amylin-activated neurons to the lateral hypothalamus

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Differential Gating and Recruitment of P/Q-, N-, and R-Type Ca²⁺Channels in Hippocampal Mossy Fiber Boutons