SUMMARY1. A tissue slice containing a section of striatum was cut obliquely from rat brain so as to preserve adjacent cortex and pallidum. Intracellular recordings were.made from 368 neurones, using either conventional or tight-seal configurations.2. Two types of neurone were distinguished electrophysiologically. Principal cells (96%) had very negative resting potentials (-89 mV) and a low input resistance at the resting membrane potential (39 MQ): membrane conductance (10 nS at -65 mV) increased within tens of milliseconds after the onset of hyperpolarization (99 nS at -120 mV). Secondary cells (4%) had less negative resting potentials (-60 mV) and a higher input resistance (117 MC2 at the resting potential): hyperpolarization caused an inward current to develop over hundreds of milliseconds that had the properties of H-current.3. Most principal cells were activated antidromically by electrical stimulation of the globus pallidus or internal capsule. Intracellular labelling with biocytin showed that principal cells had a medium sized soma (10-18 ptm), extensive dendritic trees densely studded with spines and, in some cases, a main axon which extended towards the globus pallidus.4. Electrical stimulation of the corpus callosum or external capsule evoked a depolarizing postsynaptic potential. This synaptic potential was reversibly blocked by a combination of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 /tM) and DL-2-amino-5-phosphonovaleric acid (APV, 30 #M), but was unaffected by bicuculline (30 ftM) and picrotoxin (100 ,zM). The underlying synaptic current had a fast component (time to peak about 4 ms), the amplitude of which was linearly related to membrane potential and which was blocked by CNQX; in CNQX the synaptic current had a slower component (time to peak about 10 ms) which showed voltage dependence typical of N-methyl-D-aspartate (NMDA) receptors. Both currents reversed at -5 mV.5. Focal electrical stimulation within the striatum (100-300 ,um from the site of intracellular recording) evoked a synaptic potential that was partially blocked (45-95 %) by CNQX and APV: the remaining synaptic potential was blocked by bicuculline (30 ,UM). The bicuculline-sensitive synaptic current reversed at the chloride equilibrium potential.6. The findings confirm that the majority of neostriatal neurones (principal cells, MS 8967 Z.-G. JIANG AND R. A. NORTH medium spiny neurones) project to the pallidum and receive synaptic inputs from cerebral cortex mediated by an excitatory amino acid acting through NMDA and non-NMDA receptors. These cells also receive synaptic inputs from intrinsic striatal neurones mediated by GABA. A minority of cells (4%) have distinct electrophysiological properties, also receive both types of synaptic input, and are presumed to be interneurones.

Intracellular recordings were made from neurons of rat lateral amygdala, nucleus accumbens, and striatum in vitro. Synaptic potentials mediated by Y-aminobutyric acid and by excitatory amino acids were isolated pharmacologically by using receptor antagonists, and their amplitudes were used as a measure oftransmitter release. Mucanrne and acetylcholine inhibited the release of both y-aminobutyric acid and excitatory amino acids, but measurements of the dissociation equilibrium constants for the antagonists piren- ,4]benzodiazepine-6-one, methoctramine, and hexahydrosiladifenidol indicated clearly that different muscarinic receptors were involved (MI and probably M3, respectively). The differential localization of distinct muscarinc receptor subtypes on terminals releasing the major inhibitory and excitatory transmitters of the brain could be exploited therapeutically in some movement disorders and Alzheimer disease.Acetylcholine (AcCho) has diverse functional roles in the mammalian brain, including actions at muscarinic receptors that are important for memory (1). Cholinergic neurons are lost in Alzheimer disease, and one therapeutic approach has been to develop drugs that mimic the neurotransmitter action of missing AcCho (1). However, such drugs, like AcCho itself, will have different effects at different muscarinic receptors in the brain, and not all of these effects may be desired. Three muscarinic receptors (M1-M3) can be distinguished pharmacologically, but five (ml-mS) have been identified by molecular cloning (ml-m3 correspond to M1-M3) (2-8).Fibers containing 'y-aminobutyric acid (GABA) and excitatory amino acids such as glutamate provide synaptic inputs to virtually all central neurons; therefore, in addition to their direct effects on neurons (9, 10), muscarinic agonists will also excite or inhibit cells by acting presynaptically to change release of these neurotransmitters. In the present experiments, the release of GABA and excitatory amino acids (glutamate) was assayed by recording the amplitude of depolarizing synaptic potentials from neurons in three brain regions where AcCho is known to play an important functional role-the amygdala, nucleus accumbens, and striatum. METHODSAdult rats were anesthetized with halothane and killed by a heavy blow to the chest. The brain was rapidly removed, and a block of tissue containing nucleus accumbens, dorsal striatum, or amygdaloid complex was sectioned with a Vibratome. Intracellular recordings were made from slices (300 ,am thick) by using electrodes containing 2 M KCI (11-13).The superfusing solution was a bicarbonate buffer gassed with 95% 02/5% CO2 and contained 2.5 mM KCI, 2.4 mM CaC12, 1.3 mM MgCl2, 1.2 mM NaH2PO4, 26 mM NaHCO3, 126 mM NaCi, and 10 mM glucose. The slice was completely submerged in this flowing solution, which was prewarmed to 370C. Drugs were applied by changing this solution to one that contained the drug. A bipolar tungsten-in-glass stimulating electrode was used for focal stimulation. The components of the synaptic potential...

These findings strongly suggest that STAT4 is a novel locus underlying BD. We propose a model in which up-regulation of STAT4 expression and subsequent STAT4-driven production of inflammatory cytokines, such as IL-17, constitute a potential pathway leading to BD.