Serotonin and dopamine actions on basal forebrain neurons in the ventral pallidum in vitro

Bengtson, Colin Peter (2002). Serotonin and dopamine actions on basal forebrain neurons in the ventral pallidum in vitro PhD Thesis, School of Biomedical Sciences, The University of Queensland.

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
THE16862.pdf Full text application/pdf 14.59MB 2
Author Bengtson, Colin Peter
Thesis Title Serotonin and dopamine actions on basal forebrain neurons in the ventral pallidum in vitro
School, Centre or Institute School of Biomedical Sciences
Institution The University of Queensland
Publication date 2002
Thesis type PhD Thesis
Supervisor Peregrine Osborne
Total pages 183
Language eng
Subjects 250302 Biological and Medical Chemistry
Formatted abstract
The ventral pallidum is a nucleus in the basal forebrain, which functions to guide behaviour toward reward. It contains predominantly GABA neurons that project indirectly to the prefrontal cortex and to brainstem motor nuclei via pathways of the basal ganglia. The ventral pallidum also contains cholinergic neurons, which belong to the CH4 group of the magnocellular basal forebrain. This group supplies the major acetylcholine innervations of the cortex and regulates arousal, attention and memory processes. Both neuron types are densely innervated by serotonin neurons in the dorsal raphe and by dopamine neurons in the venfral tegmental area and the substantia nigra. Dysfunction of the circuitry traversing the ventral pallidum has been implicated in the etiology of schizophrenia, obsessive-compulsive disorder and drug abuse.

This thesis presents the first in vitro study of the ventral pallidum and uses whole cell patch clamp electrophysiological techniques in brain slice preparations from immature rats. Neurobiotin filling enabled recorded neurons to be later identified and assessed for immuno-reactivity to choline acetyltransferase, a marker for cholinergic neurons. The hyperpolarisation-activated conductances of neurons were characterised in voltage clamp and correlated with their neurotransmitter content and morphological phenotype. cholinergic neurons expressed a relatively large fast inward rectifier potassium conductance while noncholinergic neurons displayed a more pronounced h-current. Noncholinergic neurons exhibited tetrodotoxin and picrotoxin sensitive inhibitory post-synaptic currents that were increased by serotonin application. It was concluded that such currents were mediated by GABAA receptors activated by synaptic input from other GABA neurons in the ventral pallidum.

Serotonin was shown to excite the vast majority of noncholinergic neurons by activating the h-current as well as a non-selective cation conductance. The 5-HT conductance was mimicked and occluded by forskolin. This result implicates the stimulation of adenyl cyclase in the 5-HT response. The pharmacological profile of this receptor was not consistent with any cloned 5-HT receptor subtype but was most similar to 5-HT6 or 5-HT7 cloned receptors. This response was sensitive to the atypical antipsychotic, clozapine.

Serotonin caused inhibitory currents in almost all cholinergic neurons in both the ventral pallidum and the globus pallidus via a 5-HT1A receptor. This 5-HT conductance involved an increase in an inward rectifier potassium conductance but was not mimicked or occluded by forskolin, implicating a cyclase independent pathway in this response. Dopamine caused excitatory currents in almost all cholinergic neurons by decreasing a potassium inward rectifier conductance. Dopamine caused excitatory currents similar to those of 5-HT and forskolm in a subset of noncholinergic neurons in the ventral pallidum. Noncholinergic neurons in the globus pallidus were characterised by various combinations of hyperpolarisation and depolarisation activated currents. Five neuronal subtypes were distinguished which were unresponsive or produced excitatory or inhibitory currents in response to serotonin.

The identification of a clozapine sensitive serotonin response of ventral pallidal GABA neurons identifies a mechanism by which this atypical antipsychotic may restore the transmission of information through the thalamus to the prefrontal cortex. The anatomical integrity of this circuit and the activation of the prefrontal cortex are compromised in schizophrenia. This 5-HT receptor is potentially novel and warrants further characterisation. The excitatory response of cholinergic neurons to dopamine suggests a direct mechanism by which the ventral tegmental area may stimulate the cholinergic release that occurs in the cortex during reward conditioning and the experience of novel stimuli. The opposing effects of dopamine and serotonin on cholinergic neurons may interact to generate the increased activity and burst firing previously demonstrated in these neurons during states of wakefulness and REM sleep. The mutual inhibition demonstrated between GABA neurons in the ventral pallidum may confer an improved spatial resolution to striatopallidal transmission and synchronise the tonic activity within this network.

Keyword Brain -- Chemistry

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
Citation counts: Google Scholar Search Google Scholar
Created: Thu, 05 Jan 2012, 11:41:05 EST by Ning Jing on behalf of The University of Queensland Library