Trends in Neurosciences
Microcircuits Special FeatureSynaptic pathways in neural microcircuits
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)
Fast inhibitory synapses: targets for neuromodulation and development of vertebrate motor behaviour
Brain Res. Rev.
(2002)- et al.
Central pattern generators deciphered by molecular genetics
Neuron
(2004) Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology
Prog. Neurobiol.
(2001)- et al.
A new class of small inhibitory interneurones in the lamprey spinal cord
Brain Res.
(1988) Neuromodulation via conditional release of endocannabinoids in the spinal locomotor network
Neuron
(2005)The multifarious hippocampal mossy fiber pathway: a review
Neuroscience
(2000)- et al.
CA1 pyramid–pyramid connections in rat hippocampus in vitro: dual intracellular recordings with biocytin filling
Neuroscience
(1996) - et al.
Dye-coupling between CA3 pyramidal cells in slices of rat hippocampus
Brain Res.
(1980) Axo-axonal coupling. a novel mechanism for ultrafast neuronal communication
Neuron
(2001)Submillisecond AMPA receptor-mediated signaling at a principal neuron–interneuron synapse
Neuron
(1997)
Interneuron diversity series: containing the detonation – feedforward inhibition in the CA3 hippocampus
Trends Neurosci.
Differences between somatic and dendritic inhibition in the hippocampus
Neuron
Short-term depression at thalamocortical synapses contributes to rapid adaptation of cortical sensory responses in vivo
Neuron
Postsynaptic pyramidal target selection by descending layer III pyramidal axons: dual intracellular recordings and biocytin filling in slices of rat neocortex
Neuroscience
Electrical synapses define networks of neocortical GABAergic neurons
Trends Neurosci.
Synaptic mechanisms of the cerebellar cortical network
Trends Neurosci.
Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex
Neuron
Tonically active GABAA receptors: modulating gain and maintaining the tone
Trends Neurosci.
Bidirectional parallel fiber plasticity in the cerebellum under climbing fiber control
Neuron
Associative short-term synaptic plasticity mediated by endocannabinoids
Neuron
Oscillations in the cerebellar cortex: a prediction of their frequency bands
Prog. Brain Res.
The motor infrastructure: from ion channels to neuronal networks
Nat. Rev. Neurosci.
Newly identified ‘glutamate interneurons’ and their role in locomotion in the lamprey spinal cord
Science
Activity-dependent metaplasticity of inhibitory and excitatory synaptic transmission in the lamprey spinal cord locomotor network
J. Neurosci.
The activity-dependent plasticity of segmental and intersegmental synaptic connections in the lamprey spinal cord
Eur. J. Neurosci.
Variable properties in a single class of excitatory spinal synapse
J. Neurosci.
Activity-dependent feedforward inhibition modulates synaptic transmission in a spinal locomotor network
J. Neurosci.
Metaplastic facilitation and ultrastructural changes in synaptic properties are associated with long-term modulation of the lamprey locomotor network
J. Neurosci.
Identification of excitatory interneurons contributing to generation of locomotion in lamprey: structure, pharmacology, and function
J. Neurophysiol.
Fast and slow locomotor burst generation in the hemispinal cord of the lamprey
J. Neurophysiol.
Mechanisms of rhythm generation in a spinal locomotor network deprived of crossed connections: the lamprey hemicord
J. Neurosci.
Excitatory synaptic drive for swimming mediated by amino acid receptors in the lamprey
J. Neurosci.
Dual-component synaptic potentials in the lamprey mediated by excitatory amino acid receptors
J. Neurosci.
Calcium-dependent potassium channels play a critical role for burst termination in the locomotor network in lamprey
J. Neurophysiol.
Modeling of substance P and 5-HT induced synaptic plasticity in the lamprey spinal CPG: consequences for network pattern generation
J. Comput. Neurosci.
Presynaptic GABAA and GABAB Receptor-mediated phasic modulation in axons of spinal motor interneurons
Eur. J. Neurosci.
The involvement of GABAB receptors and coupled G-proteins in spinal GABAergic presynaptic inhibition
J. Neurosci.
Presynaptic inhibition of synaptic transmission from sensory, interneuronal, and supraspinal neurons to spinal target cells in lamprey
Signaling mechanisms of metabotropic glutamate receptor 5 subtype and its endogenous role in a locomotor network
J. Neurosci.
Substance P modulates NMDA responses and causes long-term protein synthesis-dependent modulation of the lamprey locomotor network
J. Neurosci.
Interneurons of the hippocampus
Hippocampus
Defined types of cortical interneurone structure space and spike timing in the hippocampus
J. Physiol.
The hippocampal CA3 network: an in vivo intracellular labeling study
J. Comp. Neurol.
The time course and amplitude of EPSPs evoked at synapses between pairs of CA3/CA1 neurons in the hippocampal slice
J. Neurosci.
Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro
Annu. Rev. Neurosci.
GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus
J. Neurosci.
A frequency-dependent switch from inhibition to excitation in a hippocampal unitary circuit
Nature
Routing of spike series by dynamic circuits in the hippocampus
Nature
Synaptic excitation of inhibitory cells by single CA3 hippocampal pyramidal cells of the guinea-pig in vitro
J. Physiol.
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