Is aspartic acid the neurotransmitter of the perforant pathway?

Lauro, Andrea Di; Schmid, Rainer; Meek, James L.

doi:10.1016/0006-8993(81)90382-6

Cited by 20 publications

(2 citation statements)

References 14 publications

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“…D. Richards, personal communication). Aspartate has been a less favoured candidate for the perforant path transmitter (but see Di Lauro, Schmid & Meek, 1981). Our demonstration of stimulus-dependent release strengthens the claim of aspartate as a transmitter candidate.…”

Section: Identity Of the Perforant Path Transmittersupporting

confidence: 70%

Correlation between long‐term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats.

Bliss¹,

Douglas²,

Er̀rington³

et al. 1986

The Journal of Physiology

287

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SUMMARY1. The relationship between long-term potentiation (l.t.p.) and the release of endogenous amino acid transmitters has been investigated in the dentate gyrus of rats anaesthetized with urethane.2. The molecular layer was perfused with artificial cerebrospinal fluid using a push-pull cannula. The perfusate was collected and analysed for glutamate, aspartate, glycine, glutamine and y-aminobutyric acid (GABA) using high-performance liquid chromatography (h.p.l.c.) with fluorometric detection.3. Recording electrodes were attached to the cannula to enable responses evoked by test stimuli to the perforant path to be monitored in the molecular and cell body layers.4. Perfusion was continued for 3 h while test stimuli were delivered to the perforant path at 30 s intervals. In the control group (n = 8), no further stimulation was given. In a second group (n = 8), a single high-frequency train (250 Hz for 200 ms) was delivered at the end of the first hour to induce l.t.p. The average potentiation of the slope of the excitatory post-synaptic potential (e.p.s.p.) 2 h later was 150. In a third group (n = 8), the train to the perforant path was paired with a train to the commissural input to the dentate gyrus, a procedure which blocks the induction of l.t.p.5. In the potentiated group, there was an increase in the concentrations of glutamate and aspartate following the induction of l.t.p., relative to the decline seen in corresponding periods of the control group. This increase remained statistically significant for 1-5 h in the case of glutamate and for 45 min in the case of aspartate.6. There were no l.t.p.-associated changes in the release of glutamine or glycine; there was an indication that l.t.p. may be associated with a decrease in the release of GABA.7. Increasing the frequency and intensity of perforant path activation resulted in enhanced concentrations of glutamate and aspartate in the perfusate; no such changes occurred when granule cells were activated antidromically.8. We discuss the origin of the relative increases in the concentration of glutamate and aspartate which are found in the perfusate following the induction of l.t.p. and

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Section: Identity Of the Perforant Path Transmittersupporting

confidence: 70%

Correlation between long‐term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats.

Bliss¹,

Douglas²,

Er̀rington³

et al. 1986

The Journal of Physiology

287

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“…Several recent papers support the concept that L-aspartic acid is a neurotransmitter in the mammalian brain. This amino acid might be operative as a transmitter in (1) the perforant pathway (Di Lauro et al, 1981), (2) in the cerebellar climbing fibers (Rea et al, 1980), (3) in the hippocampal commissural fibers (Nadler et al, 1978), (4) in the lateral olfactory tract (Collins, 1979), and (5) in the cochlear fibers of auditory nerve (Wenthold and Gulley, 1977). Moreover, L-aspartate has been suggested to be the transmitter in the cone photoreceptor in the carp retina (Wu and Dowling, 1978).…”

mentioning

confidence: 99%

Specific High‐Affinity Binding of L‐[³H]Aspartate to Rat Brain Membranes

Lauro

Meek

Costa

1982

Journal of Neurochemistry

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The binding of L-[3H]aspartate was investigated in washed membranes prepared from whole rat brain. We were able to differentiate two separate binding sites differing in their Na dependence. The Na-independent binding was saturable, reversible, and optimal at 20 degrees C and at pHs in the neutral range. The dissociation constant (Kd) at 20 degrees C was about 200 nM. This binding site seemed to be modulated by magnesium and calcium at physiological concentrations. None of the amino acids tested was a potent competitor for Na-independent L-[3H]aspartate binding. This binding site was unevenly distributed in the rat central nervous system: cerebellum = cerebral cortex greater than pons-medulla greater than spinal cord. Destruction of the intrinsic neurons of the cerebellum by injecting kainic acid 30 days before sacrifice resulted in a 53% reduction in Na-independent binding in this region. The Na-dependent binding of L-[3H]-aspartate (Kd = 4894 nM) was strongly inhibited by D-aspartate, L-glutamate, D,L-aspartate beta-hydroxamate; was unaffected by calcium and magnesium; and showed a different pattern of distribution: cerebral cortex greater than cerebellum = pons-medulla = spinal cord. This binding in cerebellum was unaffected by injections of kainic acid.

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Connection matrix of the hippocampal formation: I. The dentate gyrus

1995

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The hippocampal formation presents a special opportunity for realistic neural modeling since its structure, connectivity, and physiology are better understood than that of other cortical components. A review of the quantitative neuroanatomy of the rodent dentate gyrus (DG) is presented in the context of the development of a computational model of its connectivity. The DG is a three-layered folded sheet of neural tissue. This sheet is represented as a rectangle, having a surface area of 37 mm2 and a septotemporal length of 12 mm. Points, representing cell somata, are distributed in the model rectangle in a roughly uniform fashion. Synaptic connectivity is generated by assigning each presynaptic cell a spatial zone representing its axonal arbor. For each postsynaptic cell, a list of potential presynaptic cells is compiled, based on which arbor zones the given postsynaptic cell falls within. An appropriate number of presynaptic inputs are then selected at random. The principal cells of the DG, the granule cells, are represented in the model, as are non-principal cells, including basket cells, chandelier cells, mossy cells, and GABAergic peptidergic polymorphic (GPP) cells. The neurons of layer II of the entorhinal cortex are included also. The DG receives its main extrinsic input from these cells via the perforant path. The basket cells, chandelier cells, and GPP cells receive perforant path and granule cell input and exert both feedforward and feedback inhibition onto the granule cells. Mossy cells receive converging input from granule cells and send their output back primarily to distant septotemporal levels, where they contact both granule cells and non-principal cells. To permit numerical simulations, the model must be scaled down while preserving its anatomical structure. A variety of methods for doing this exist. Hippocampal allometry provides valuable clues in this regard.

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Is aspartic acid the neurotransmitter of the perforant pathway?

Cited by 20 publications

References 14 publications

Correlation between long‐term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats.

Correlation between long‐term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats.

Specific High‐Affinity Binding of L‐[³H]Aspartate to Rat Brain Membranes

Connection matrix of the hippocampal formation: I. The dentate gyrus

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Is aspartic acid the neurotransmitter of the perforant pathway?

Cited by 20 publications

References 14 publications

Correlation between long‐term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats.

Correlation between long‐term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats.

Specific High‐Affinity Binding of L‐[3H]Aspartate to Rat Brain Membranes

Connection matrix of the hippocampal formation: I. The dentate gyrus

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Specific High‐Affinity Binding of L‐[³H]Aspartate to Rat Brain Membranes