64 research outputs found
Physiological Properties of Cholinergic and Non-Cholinergic Magnocellular Neurons in Acute Slices from Adult Mouse Nucleus Basalis
The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown.Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70-80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 64+/-3.4 and 75+/-2 mV; half widths 0.52+/-0.04 and 0.33+/-0.02 ms). Cholinergic neurons displayed a more pronounced slow after-hyperpolarization than non-cholinergic neurons (13.3+/-2.2 and 3.6+/-0.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of approximately 20 Hz and >120 Hz).Our results indicate that neurons in nucleus basalis share similar physiological properties with neurons in anterior regions of the basal forebrain. Furthermore, cholinergic and non-cholinergic neurons in nucleus basalis can be distinguished by their responses to injected current. To our knowledge, this is the first description of the physiological properties of cholinergic and non-cholinergic neurons in the posterior aspects of the basal forebrain complex and the first study of basal forebrain neurons from the mouse
Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking.
The ventral pallidum is centrally positioned within mesocorticolimbic reward circuits, and its dense projection to the ventral tegmental area (VTA) regulates neuronal activity there. However, the ventral pallidum is a heterogeneous structure, and how this complexity affects its role within wider reward circuits is unclear. We found that projections to VTA from the rostral ventral pallidum (RVP), but not the caudal ventral pallidum (CVP), were robustly Fos activated during cue-induced reinstatement of cocaine seeking--a rat model of relapse in addiction. Moreover, designer receptor-mediated transient inactivation of RVP neurons, their terminals in VTA or functional connectivity between RVP and VTA dopamine neurons blocked the ability of drug-associated cues (but not a cocaine prime) to reinstate cocaine seeking. In contrast, CVP neuronal inhibition blocked cocaine-primed, but not cue-induced, reinstatement. This double dissociation in ventral pallidum subregional roles in drug seeking is likely to be important for understanding the mesocorticolimbic circuits underlying reward seeking and addiction
Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders
There is a long-standing paradox that N-methyl-D-aspartate receptors (NMDARs) can both promote neuronal health and kill neurons. Recent studies show that NMDAR-induced responses depend on the receptor location: stimulation of synaptic NMDARs, acting primarily through nuclear Ca(2+) signaling, leads to the build-up of a neuroprotective ‘shield’, whereas stimulation of extrasynaptic NMDARs promotes cell death. These differences result from the activation of distinct genomic programmes and opposing actions on intracellular signalling pathways. Perturbations in the balance between synaptic and extrasynaptic NMDAR activity contribute to neuronal dysfunction in acute ischaemia and Huntington’s disease and could be a common theme in the aetiology of neurodegenerative diseases. Neuroprotective therapies should aim to both enhance the effect of synaptic activity and disrupt extrasynaptic NMDAR-dependent death signalling
Voltage-gated calcium channels mediate intracellular calcium increase in weaver dopaminergic neurons during stimulation of D2 and GABAB receptors.
Voltage-gated calcium channels mediate intracellular calcium
increase in weaver dopaminergic neurons during stimulation of
D2 and GABAB receptors. J Neurophysiol 92: 3368–3374, 2004. First
published July 7, 2004; doi:10.1152/jn.00602.2004. The weaver (wv)
mutation affects the pore-forming region of the inwardly rectifying
potassium channel (GIRK) leading to degeneration of cerebellar
granule and midbrain dopaminergic neurons. The mutated channel
(wvGIRK) loses its potassium selectivity, allowing sodium (Na) and
possibly calcium ions (Ca2) to enter the cell. Here we performed
whole cell patch-clamp recordings combined with microfluorometry
to investigate possible differences in calcium ([Ca2]i) dynamics in
native dopaminergic neurons (expressing the wvGIRK2 subunits) in
the midbrain slice preparation from homozygous weaver (wv/wv) and
control (/) mice. Under resting conditions, [Ca2]i was similar in
wv/wv compared with / neurons. Activation of wvGIRK2 channels
by D2 and GABAB receptors increased [Ca2]i in wv/wv neurons,
whereas activation of wild-type channels decreased [Ca2]i in /
neurons. The calcium rise in wv/wv neurons was abolished by antagonists
of the voltage-gated calcium channels (VGCC); voltage clamp
of the neuron at 60 mV; and hyperpolarization of the neuron to 80
mV or more, in current clamp, and was unaffected by TTX. Therefore
we propose that wvGIRK2 channels in native dopamine neurons are
not permeable to Ca2, and when activated by D2 and GABAB
receptors they mediate membrane depolarization and an indirect Ca2
influx through VGCC rather than via wvGIRK2 channels. Such
calcium influx may be the trigger for calcium-mediated excitotoxicity,
responsible for selective neuronal death in weaver mic
Physical Repercussions of Childhood-Onset Growth Hormone (GH) Deficiency and hGH Treatment in Adulthood
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