Marco Capogna

Differential modulation of excitatory and inhibitory striatal synaptic transmission by histamine

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Tommas J Ellender, MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, OX1 3TH, Oxford, United Kingdom.
  • ,
  • Icnelia Huerta-Ocampo
  • ,
  • Karl Deisseroth
  • ,
  • Marco Capogna
  • J Paul Bolam

Information processing in the striatum is critical for basal ganglia function and strongly influenced by neuromodulators (e.g., dopamine). The striatum also receives modulatory afferents from the histaminergic neurons in the hypothalamus which exhibit a distinct diurnal rhythm with high activity during wakefulness, and little or no activity during sleep. In view of the fact that the striatum also expresses a high density of histamine receptors, we hypothesized that released histamine will affect striatal function. We studied the role of histamine on striatal microcircuit function by performing whole-cell patch-clamp recordings of neurochemically identified striatal neurons combined with electrical and optogenetic stimulation of striatal afferents in mouse brain slices. Bath applied histamine had many effects on striatal microcircuits. Histamine, acting at H(2) receptors, depolarized both the direct and indirect pathway medium spiny projection neurons (MSNs). Excitatory, glutamatergic input to both classes of MSNs from both the cortex and thalamus was negatively modulated by histamine acting at presynaptic H(3) receptors. The dynamics of thalamostriatal, but not corticostriatal, synapses were modulated by histamine leading to a facilitation of thalamic input. Furthermore, local inhibitory input to both classes of MSNs was negatively modulated by histamine. Subsequent dual whole-cell patch-clamp recordings of connected pairs of striatal neurons revealed that only lateral inhibition between MSNs is negatively modulated, whereas feedforward inhibition from fast-spiking GABAergic interneurons onto MSNs is unaffected by histamine. These findings suggest that the diurnal rhythm of histamine release entrains striatal function which, during wakefulness, is dominated by feedforward inhibition and a suppression of excitatory drive.

Original languageEnglish
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Pages (from-to)15340-51
Number of pages12
Publication statusPublished - 26 Oct 2011

    Research areas

  • Animals, Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics, Channelrhodopsins, Corpus Striatum/cytology, Electric Stimulation, Excitatory Amino Acid Agents/pharmacology, Excitatory Postsynaptic Potentials/drug effects, Feedback, Physiological/drug effects, Female, GABA Agents/pharmacology, Green Fluorescent Proteins/genetics, Hippocampus/physiology, Histamine/metabolism, Histamine Agonists/metabolism, Histamine Antagonists/pharmacology, In Vitro Techniques, Inhibitory Postsynaptic Potentials/drug effects, Male, Mice, Mice, Transgenic, Mutation/genetics, Neural Inhibition/drug effects, Neural Pathways/physiology, Neurons/drug effects, Parvalbumins/metabolism, Patch-Clamp Techniques/methods, Piperidines/pharmacology, Receptors, Dopamine D1/genetics, Receptors, Dopamine D2/genetics, Synaptic Transmission/drug effects, Thalamus/physiology, Transfection/methods, Tyrosine 3-Monooxygenase/metabolism, Vesicular Glutamate Transport Protein 1/metabolism, Vesicular Inhibitory Amino Acid Transport Proteins/metabolism

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