Trends in Neurosciences
Volume 28, Issue 10, October 2005, Pages 541-551
Journal home page for Trends in Neurosciences

Microcircuits Special Feature
Synaptic pathways in neural microcircuits

https://doi.org/10.1016/j.tins.2005.08.004Get rights and content

The functions performed by different neural microcircuits depend on the anatomical and physiological properties of the various synaptic pathways connecting neurons. Neural microcircuits across various species and brain regions are similar in terms of their repertoire of neurotransmitters, their synaptic kinetics, their short-term and long-term plasticity, and the target-specificity of their synaptic connections. However, microcircuits can be fundamentally different in terms of the precise recurrent design used to achieve a specific functionality. In this review, which is part of the TINS Microcircuits Special Feature, we compare the connectivity designs in spinal, hippocampal, neocortical and cerebellar microcircuits, and discuss the different computational challenges that each microcircuit faces.

Introduction

Neural microcircuits* are fascinating because they generate a ‘life of their own’. These emergent states take on many different forms, depending on the cellular and synaptic design of the microcircuit. Microcircuits are similar in that they use excitatory and inhibitory neurons interconnected with dynamic synapses to embed inherited information on how to execute specific behaviours. Specific microcircuits are also surprisingly similar across different species. Microcircuits can be constructed to produce autonomous rhythmic behaviour (in the spinal cord), to relay and transform information to build maps of associations between parameters of the world (in the hippocampus), to predict events and deal with real-time updates (in the neocortex), or to compute error functions of the mismatch between the predicted and the actual world (in the cerebellum). In this review, the basic designs of the lamprey spinal cord microcircuit, and of the mammalian hippocampal, neocortical and cerebellar microcircuits, are presented in a highly condensed form. The aim is not to cover comprehensively the microcircuits of each of these brain regions, but to give a flavour of the differences and similarities in the microcircuit designs. The computational challenges that each microcircuit faces are also discussed.

Section snippets

Synaptic transmission in the spinal locomotor network

In all vertebrates, locomotion is coordinated by spinal networks referred to as central pattern generators (CPGs) (for a recent review, see [1]). We will use the synaptic interaction within the lamprey CPG as a model because it is currently the best understood adult microcircuit, but important information is also available from the developing nervous systems of amphibians and rodents 2, 3. The spinal networks consist of motoneurons and various types of interneurons 1, 4, 5, 6, 7, 8, 9, 10, 11.

Synaptic transmission in the hippocampus

The mammalian hippocampus can be subdivided into CA3, CA2 and CA1 subfields, and excellent reviews describe the circuitry in detail 26, 27. A simplified circuit diagram showing some of the major synaptic connections in the hippocampus is illustrated in Figure 2 (see also Grillner et al., in this issue).

Several excitatory neuron to excitatory neuron (E–E) connections exist in the hippocampus, where information processed by the dentate gyrus projects to CA3 pyramidal cells via mossy fibres (MFs),

Synaptic transmission in the neocortex

The mammalian neocortex is composed of 6 layers, with interneurons in all layers, pyramidal cells in layers L2–L6 and spiny stellate cells (SSCs) in L4 of primary sensory cortices. As in the hippocampus, pyramidal cells are the principal cells of the neocortex, and these excitatory glutamatergic neurons comprise ∼80% of neocortical neurons.

Thalamic input enters primarily into L4 (the first station of sensory processing) targeting SSCs [49], other neurons, and dendrites of neurons that pass

Synaptic transmission in the cerebellum

The mammalian cerebellum is faced with the problem of processing information conveyed by an immense number of input fibres (estimated at ∼40 million in humans) such that the processed signal can be transmitted over output fibres less numerous by a factor of 40. This task conceivably requires a neuron type able to receive myriad synapses (the Purkinje cell), pre-processing of the input (performed within the granular layer), and a learning mechanism that enables input patterns worth processing

Speculations

The spinal, hippocampal, neocortical and cerebellar microcircuits have much in common: they all rely on interactions between excitatory and inhibitory neurons to perform computations; they all use glutamate for excitation; they use GABA for inhibition (except in the spinal cord locomotor microcircuit, where glycine is used); and their synapses all display variable synaptic dynamics. However, these microcircuits are fundamentally different in many respects. The spinal cord relies on a network of

Acknowledgements

We gratefully acknowledge support from EU grant QlG3-CT-2001-01241, the Swedish Research Council, and an HFSP grant to G.S, and Dr David Parker for help in the preparation of figures.

References (108)

  • J.J. Lawrence et al.

    Interneuron diversity series: containing the detonation – feedforward inhibition in the CA3 hippocampus

    Trends Neurosci.

    (2003)
  • R. Miles

    Differences between somatic and dendritic inhibition in the hippocampus

    Neuron

    (1996)
  • S. Chung

    Short-term depression at thalamocortical synapses contributes to rapid adaptation of cortical sensory responses in vivo

    Neuron

    (2002)
  • A.M. Thomson et al.

    Postsynaptic pyramidal target selection by descending layer III pyramidal axons: dual intracellular recordings and biocytin filling in slices of rat neocortex

    Neuroscience

    (1998)
  • S. Hestrin et al.

    Electrical synapses define networks of neocortical GABAergic neurons

    Trends Neurosci.

    (2005)
  • S. Nakanishi

    Synaptic mechanisms of the cerebellar cortical network

    Trends Neurosci.

    (2005)
  • M. Hamann

    Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex

    Neuron

    (2002)
  • A. Semyanov

    Tonically active GABAA receptors: modulating gain and maintaining the tone

    Trends Neurosci.

    (2004)
  • M. Coesmans

    Bidirectional parallel fiber plasticity in the cerebellum under climbing fiber control

    Neuron

    (2004)
  • S.D. Brenowitz et al.

    Associative short-term synaptic plasticity mediated by endocannabinoids

    Neuron

    (2005)
  • R. Maex et al.

    Oscillations in the cerebellar cortex: a prediction of their frequency bands

    Prog. Brain Res.

    (2005)
  • S. Grillner

    The motor infrastructure: from ion channels to neuronal networks

    Nat. Rev. Neurosci.

    (2003)
  • J.T. Buchanan et al.

    Newly identified ‘glutamate interneurons’ and their role in locomotion in the lamprey spinal cord

    Science

    (1987)
  • D. Parker et al.

    Activity-dependent metaplasticity of inhibitory and excitatory synaptic transmission in the lamprey spinal cord locomotor network

    J. Neurosci.

    (1999)
  • D. Parker et al.

    The activity-dependent plasticity of segmental and intersegmental synaptic connections in the lamprey spinal cord

    Eur. J. Neurosci.

    (2000)
  • D. Parker

    Variable properties in a single class of excitatory spinal synapse

    J. Neurosci.

    (2003)
  • D. Parker

    Activity-dependent feedforward inhibition modulates synaptic transmission in a spinal locomotor network

    J. Neurosci.

    (2003)
  • S. Bevan et al.

    Metaplastic facilitation and ultrastructural changes in synaptic properties are associated with long-term modulation of the lamprey locomotor network

    J. Neurosci.

    (2004)
  • J.T. Buchanan

    Identification of excitatory interneurons contributing to generation of locomotion in lamprey: structure, pharmacology, and function

    J. Neurophysiol.

    (1989)
  • L. Cangiano et al.

    Fast and slow locomotor burst generation in the hemispinal cord of the lamprey

    J. Neurophysiol.

    (2003)
  • L. Cangiano et al.

    Mechanisms of rhythm generation in a spinal locomotor network deprived of crossed connections: the lamprey hemicord

    J. Neurosci.

    (2005)
  • N. Dale

    Excitatory synaptic drive for swimming mediated by amino acid receptors in the lamprey

    J. Neurosci.

    (1986)
  • N. Dale et al.

    Dual-component synaptic potentials in the lamprey mediated by excitatory amino acid receptors

    J. Neurosci.

    (1986)
  • A. El Manira

    Calcium-dependent potassium channels play a critical role for burst termination in the locomotor network in lamprey

    J. Neurophysiol.

    (1994)
  • Biro, Z. et al. (2003) 5-HT modulation of excitatory interneurons in the lamprey spinal cord. Program number 188.7. In...
  • A. Kozlov

    Modeling of substance P and 5-HT induced synaptic plasticity in the lamprey spinal CPG: consequences for network pattern generation

    J. Comput. Neurosci.

    (2001)
  • S. Alford

    Presynaptic GABAA and GABAB Receptor-mediated phasic modulation in axons of spinal motor interneurons

    Eur. J. Neurosci.

    (1991)
  • S. Alford et al.

    The involvement of GABAB receptors and coupled G-proteins in spinal GABAergic presynaptic inhibition

    J. Neurosci.

    (1991)
  • A. El Manira

    Presynaptic inhibition of synaptic transmission from sensory, interneuronal, and supraspinal neurons to spinal target cells in lamprey

  • P. Kettunen

    Signaling mechanisms of metabotropic glutamate receptor 5 subtype and its endogenous role in a locomotor network

    J. Neurosci.

    (2002)
  • D. Parker

    Substance P modulates NMDA responses and causes long-term protein synthesis-dependent modulation of the lamprey locomotor network

    J. Neurosci.

    (1998)
  • T.F. Freund et al.

    Interneurons of the hippocampus

    Hippocampus

    (1996)
  • P. Somogyi et al.

    Defined types of cortical interneurone structure space and spike timing in the hippocampus

    J. Physiol.

    (2005)
  • X.G. Li

    The hippocampal CA3 network: an in vivo intracellular labeling study

    J. Comp. Neurol.

    (1994)
  • R.J. Sayer

    The time course and amplitude of EPSPs evoked at synapses between pairs of CA3/CA1 neurons in the hippocampal slice

    J. Neurosci.

    (1990)
  • R.D. Traub

    Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro

    Annu. Rev. Neurosci.

    (2004)
  • L. Acsady

    GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus

    J. Neurosci.

    (1998)
  • M. Mori

    A frequency-dependent switch from inhibition to excitation in a hippocampal unitary circuit

    Nature

    (2004)
  • F. Pouille et al.

    Routing of spike series by dynamic circuits in the hippocampus

    Nature

    (2004)
  • R. Miles

    Synaptic excitation of inhibitory cells by single CA3 hippocampal pyramidal cells of the guinea-pig in vitro

    J. Physiol.

    (1990)
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