Unilateral lesion of the nigrostriatal pathway decreases the response of fast-spiking interneurons in the medial prefrontal cortex to 5-HT1A receptor agonist and expression of the receptor in parvalbumin-positive neurons in the rat

5-Hydroxytryptamine(1A) (5-HT(1A)) receptors are expressed in the prefrontal cortical interneurons. Among these interneurons, calcium-binding protein parvalbumin (PV)-positive fast spiking (FS) interneurons play an important role in regulatory function of the prefrontal cortex. In the present study, the response of medial prefrontal cortex (mPFC) FS interneurons to the selective 5-HT(1A) receptor agonist 8-OH-DPAT and change in expression of 5-HT(1A) receptor on PV-positive neurons were examined in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) by using extracellular recording and double-labeling immunofluorescence histochemistry. Systemic administration of 8-OH-DPAT (1-243 μg/kg, i.v.) dose-dependently inhibited the mean firing rate of the FS interneurons in sham-operated and the lesioned rats, respectively. The cumulative doses producing inhibition in the lesioned rats (243 μg/kg) was significantly higher than that of sham-operated rats (27 μg/kg). Furthermore, the local application of 8-OH-DPAT (0.01 μg) in the mPFC inhibited the FS interneurons in sham-operated rats, while having no effect on firing rate of the FS interneurons in the lesioned rats. In contrast to sham-operated rats, the lesion of the SNc in rats did not cause the change of PV-positive neurons in the prelimbic prefrontal cortex, a subregion of the mPFC, whereas the lesion of the SNc markedly reduced in percentage of PV-positive neurons expressing 5-HT(1A) receptors. Our results indicate that degeneration of the nigrostriatal pathway results in the decreased response of FS interneurons in the mPFC to 5-HT(1A) receptor stimulation, which attributes to down-regulation of 5-HT(1A) receptor expression in these interneurons.

[1]  Jian Liu,et al.  In vivo effects of activation and blockade of 5-HT2A/2C receptors in the firing activity of pyramidal neurons of medial prefrontal cortex in a rodent model of Parkinson's disease , 2009, Experimental Neurology.

[2]  F. Zhou,et al.  Activation of serotonin receptors modulates synaptic transmission in rat cerebral cortex. , 1999, Journal of neurophysiology.

[3]  Jordi Serrats,et al.  Expression of serotonin1A and serotonin2A receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex. , 2004, Cerebral cortex.

[4]  P. Goldman-Rakic,et al.  Correlated discharges among putative pyramidal neurons and interneurons in the primate prefrontal cortex. , 2002, Journal of neurophysiology.

[5]  G. Aghajanian,et al.  Serotonin Induces Excitatory Postsynaptic Potentials in Apical Dendrites of Neocortical Pyramidal Cells , 1997, Neuropharmacology.

[6]  L. Chen,et al.  The firing activity of pyramidal neurons in medial prefrontal cortex and their response to 5-hydroxytryptamine-1A receptor stimulation in a rat model of Parkinson's disease , 2009, Neuroscience.

[7]  G. Gessa,et al.  6‐Hydroxydopamine lesion in the ventral tegmental area fails to reduce extracellular dopamine in the cerebral cortex , 2008, Journal of neuroscience research.

[8]  T. Branchek,et al.  A receptor autoradiographic and in situ hybridization analysis of the distribution of the 5‐ht7 receptor in rat brain , 1996, British journal of pharmacology.

[9]  Marcus C. Ferguson,et al.  Cortical serotonin and norepinephrine denervation in parkinsonism: preferential loss of the beaded serotonin innervation , 2009, The European journal of neuroscience.

[10]  Y. Khan,et al.  Cellular distribution of dopamine D1 and D2 receptors in rat medial prefrontal cortex , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  D. Brooks,et al.  Tremor in Parkinson’s disease and serotonergic dysfunction , 2003, Neurology.

[12]  Y. Kubota,et al.  GABAergic cell subtypes and their synaptic connections in rat frontal cortex. , 1997, Cerebral cortex.

[13]  J. Neumaier,et al.  Localization of 5-HT7 receptors in rat brain by immunocytochemistry, in situ hybridization, and agonist stimulated cFos expression , 2001, Journal of Chemical Neuroanatomy.

[14]  H. Steinbusch,et al.  Distribution of serotonin-immunoreactivity in the central nervous system of the rat—Cell bodies and terminals , 1981, Neuroscience.

[15]  H. Markram,et al.  Interneurons of the neocortical inhibitory system , 2004, Nature Reviews Neuroscience.

[16]  M. Celio,et al.  Parvalbumin in most gamma-aminobutyric acid-containing neurons of the rat cerebral cortex. , 1986, Science.

[17]  Y. Kawaguchi,et al.  Two distinct activity patterns of fast-spiking interneurons during neocortical UP states , 2008, Proceedings of the National Academy of Sciences.

[18]  V. Kostic,et al.  Depression and parkinson's disease: possible role of serotonergic mechanisms , 1987, Journal of Neurology.

[19]  I. V. Tetko,et al.  Different tonic regulation of neuronal activity in the rat dorsal raphe and medial prefrontal cortex via 5-HT1A receptors , 2001, Neuroscience Letters.

[20]  M. Gernert,et al.  Altered spontaneous discharge rate and pattern of basal ganglia output neurons in the circling (ci2) rat mutant , 2003, Neuroscience.

[21]  Jens Volkmann,et al.  Depression and Parkinson’s disease , 2004, Journal of Neurology.

[22]  Rex Y. Wang,et al.  Electrophysiological evidence for a functional interaction between 5‐HT1A and 5‐HT2A receptors in the rat medial prefrontal cortex: An lontophoretic study , 1994, Synapse.

[23]  G. Mengod,et al.  Serotonin 1A receptors in human and monkey prefrontal cortex are mainly expressed in pyramidal neurons and in a GABAergic interneuron subpopulation: implications for schizophrenia and its treatment , 2008, Journal of neurochemistry.

[24]  P. Celada,et al.  Involvement of 5-HT1A Receptors in Prefrontal Cortex in the Modulation of Dopaminergic Activity: Role in Atypical Antipsychotic Action , 2005, The Journal of Neuroscience.

[25]  M. Pompeiano,et al.  Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. , 1994, Brain research. Molecular brain research.

[26]  Y. Agid,et al.  Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease , 1983, Brain Research.

[27]  M. Celio,et al.  Calbindin D-28k and parvalbumin in the rat nervous system , 1990, Neuroscience.

[28]  Y. Kawaguchi,et al.  Parvalbumin, somatostatin and cholecystokinin as chemical markers for specific GABAergic interneuron types in the rat frontal cortex , 2002, Journal of neurocytology.

[29]  M. Pompeiano,et al.  Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  R. Oades,et al.  Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity , 1987, Brain Research Reviews.

[31]  Trevor Sharp,et al.  A review of central 5-HT receptors and their function , 1999, Neuropharmacology.

[32]  R. Miller,et al.  Calcium buffering properties of calbindin D28k and parvalbumin in rat sensory neurones. , 1993, The Journal of physiology.

[33]  Françoise Condé,et al.  Local circuit neurons immunoreactive for calretinin, calbindin D‐28k or parvalbumin in monkey prefronatal cortex: Distribution and morphology , 1994, The Journal of comparative neurology.

[34]  E. V. Bockstaele,et al.  Topography of serotonin neurons in the dorsal raphe nucleus that send axon collaterals to the rat prefrontal cortex and nucleus accumbens , 1993, Brain Research.

[35]  Fred H. Gage,et al.  Partial lesion of the substantia nigra: relation between extent of lesion and rotational behavior , 1991, Brain Research.

[36]  J. Schwartz,et al.  Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Y. Wang,et al.  In vivo modulation of the firing activity of putative slow- and fast-spiking interneurons in the medial prefrontal cortex by 5-HT3 receptors in 6-hydroxydopamine-induced Parkinsonian rats , 2010, Neuroscience.

[38]  G. Aghajanian,et al.  Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release , 1999, Brain Research.

[39]  A. Kingsbury,et al.  Post-synaptic 5-HT1A and 5-HT2A receptors are increased in Parkinson's disease neocortex. , 1998, Annals of the New York Academy of Sciences.

[40]  Y. Ohno.  New insight into the therapeutic role of 5-HT1A receptors in central nervous system disorders. , 2010, Central nervous system agents in medicinal chemistry.

[41]  E. Callaway,et al.  Immunochemical characterization of inhibitory mouse cortical neurons: Three chemically distinct classes of inhibitory cells , 2010, The Journal of comparative neurology.

[42]  Á. Pazos,et al.  5-HT1B receptor binding in degenerative movement disorders , 1998, Brain Research.

[43]  D. Lewis,et al.  Parvalbumin-positive basket interneurons in monkey and rat prefrontal cortex. , 2008, Journal of neurophysiology.

[44]  P. Svenningsson,et al.  Changes on 5-HT2 receptor mRNAs in striatum and subthalamic nucleus in Parkinson's disease model , 2007, Physiology & Behavior.

[45]  F. Benes,et al.  Cellular colocalization of dopamine D1 and D2 receptors in rat medial prefrontal cortex , 1995, Synapse.

[46]  R. Andrade,et al.  5-Hydroxytryptamine2 and 5-hydroxytryptamine1A receptors mediate opposing responses on membrane excitability in rat association cortex , 1991, Neuroscience.

[47]  M. Hajós,et al.  In vivo inhibition of neuronal activity in the rat ventromedial prefrontal cortex by midbrain-raphe nuclei: role of 5-HT1A receptors , 2003, Neuropharmacology.

[48]  G. Knudsen,et al.  The 5-HT1A serotonin receptor is located on calbindin- and parvalbumin-containing neurons in the rat brain , 2003, Brain Research.

[49]  A L Benabid,et al.  Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal activity of the pedunculopontine nucleus, which is reversed by the lesion of the subthalamic nucleus in the rat , 2001, The European journal of neuroscience.

[50]  R. Insausti,et al.  Serotonin 5‐HT1A receptor expression is selectively enhanced in the striosomal compartment of chronic parkinsonian monkeys , 2001, Synapse.

[51]  J. Fuster.  The Prefrontal Cortex , 1997 .

[52]  P. Wong,et al.  Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats , 2005, Brain Research.

[53]  T. Araki,et al.  Cerebral alterations in a MPTP-mouse model of Parkinson’s disease – an immunocytochemical study , 2003, Journal of Neural Transmission.

[54]  P. Celada,et al.  In vivo excitation of GABA interneurons in the medial prefrontal cortex through 5-HT3 receptors. , 2004, Cerebral cortex.

[55]  F. Bloom,et al.  The 5-HT3 Receptor Is Present in Different Subpopulations of GABAergic Neurons in the Rat Telencephalon , 1997, The Journal of Neuroscience.

[56]  Kuei Yuan Tseng,et al.  Excitatory response of prefrontal cortical fast‐spiking interneurons to ventral tegmental area stimulation in vivo , 2006, Synapse.

[57]  P. Jenner,et al.  Reduction in cortical 5-HT3 binding sites following a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle in rats , 1993, Journal of the Neurological Sciences.

[58]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[59]  D. Lewis,et al.  Cortical inhibitory neurons and schizophrenia , 2005, Nature Reviews Neuroscience.

[60]  B. Rudy,et al.  Perisomatic GABA Release and Thalamocortical Integration onto Neocortical Excitatory Cells Are Regulated by Neuromodulators , 2008, Neuron.

[61]  M. Marín‐padilla.  Double origin of the pericellular baskets of the pyramidal cells of the human motor cortex: a Golgi study. , 1969, Brain research.

[62]  Y. Kawaguchi,et al.  Serotonin Modulates Fast-Spiking Interneuron and Synchronous Activity in the Rat Prefrontal Cortex through 5-HT1A and 5-HT2A Receptors , 2010, The Journal of Neuroscience.

[63]  Y. Wang,et al.  Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal firing of the midbrain raphe nuclei 5-HT neurons and a decrease of their response to 5-HT1A receptor stimulation in the rat , 2009, Neuroscience.

[64]  Y. Kubota,et al.  Three distinct subpopulations of GABAergic neurons in rat frontal agranular cortex , 1994, Brain Research.

[65]  J. Burgunder,et al.  Modulation of parvalbumin expression in the motor cortex of parkinsonian rats , 2005, Experimental Neurology.

[66]  J. Mitrofanis,et al.  Reduction in parvalbumin expression in the zona incerta after 6OHDA lesion in rats , 2005, Journal of neurocytology.

[67]  J. M. Araujo-Alvarez,et al.  In vivo effects of local activation and blockade of 5-HT1B receptors on globus pallidus neuronal spiking , 2005, Brain Research.

[68]  G. M. Halliday,et al.  Loss of brainstem serotonin- and substance P-containing neurons in Parkinson's disease , 1990, Brain Research.

[69]  T. Araki,et al.  Protective effects of neuronal nitric oxide synthase inhibitor in mouse brain against MPTP neurotoxicity: an immunohistological study , 2004, European Neuropsychopharmacology.

[70]  P. Celada,et al.  Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. , 2004, Cerebral cortex.

[71]  Grzegorz Hess,et al.  5-HT7 receptors increase the excitability of rat hippocampal CA1 pyramidal neurons , 2003, Brain Research.