Neuroanatomy of the dopaminergic system

Nature Reviews Neuroscience 9, 326. May 2008 | doi:10.1038/nrn2381
The ventral tegmental area contains two distinct types of dopaminergic neuron.

Dopamine is a versatile neurotransmitter that has a role in movement and many aspects of cognition. Lammel et al. have now characterized two types of neurons in the mesocorticolimbic dopamine system that are not only anatomically segregated, with non-overlapping axonal target regions, but that also have distinct molecular and functional properties. This structured diversity of the dopamine midbrain system might contribute to the multiplicity of dopamine functions in the CNS.
Dopamine pathways in the brain are generally divided into the well-characterized mesostriatal system, which originates in the substantia nigra pars compacta (SNc) and projects to the dorsal striatum, and the mesocorticolimbic system, which starts in the ventral tegmental area (VTA) and projects to the frontal cortex and limbic areas including the amygdala and the nucleus accumbens (NAc). By retrogradely tracing mesocorticolimbic dopamine neurons, the authors established that dopamine projections in the medial prefrontal cortex, the basolateral amygdala and the core and medial shell of the NAc originate in the medial posterior part of the VTA, whereas dopamine projections to the lateral shell of the NAc originate in the more lateral portions of the VTA and the medial part of the SNc.

ORIGINAL RESEARCH PAPER
Lammel, S. et al. Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron 57, 760–773 (2008). Pubmed

Parkinson’s Disease and Olfaction

Kranick SM, & Duda JE. Olfactory dysfunction in Parkinson’s disease. Neurosignals. 2008; 16(1): 35-40.

Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Abstract

Prior to the onset of the cardinal motor features of idiopathic Parkinson’s disease (PD), other manifestations of neurodegeneration such as olfactory dysfunction are often apparent. Characterizing these potential biomarkers of preclinical PD is particularly important in identifying individuals who will go on to develop disabling symptoms, and thus be good candidates for new neuroprotective strategies. As shown by the Braak neuropathologic staging of PD, the olfactory system is among the first neuronal populations to display Lewy body pathology. Clinically, loss of smell can be easily tested in the office using several validated techniques and is often helpful to the physician in distinguishing idiopathic PD from other forms of parkinsonism. Recent findings have indicated that a decline in olfaction may be observed in selected at-risk patients, which has significant implications for identifying potential study populations. Ongoing studies of olfactory dysfunction may also reveal potential for use as a medication-independent biomarker of disease progression in addition to use as a biomarker for the diagnosis of PD.

Pubmed link

A New, Genetic Model for Schizophrenia

A new study points to rare gene duplications and deletions that are believed to play a significant role in the psychological disorder
By Nikhil Swaminathanin Scientific American

A new study indicates that the genetic culprits behind schizophrenia may be much less common than previously believed. Researchers report this week in Science that a rare but devastating change in one of several different genes may dramatically increase the risk of developing the debilitating brain disorder affecting 1 percent of the world’s population and marked by psychotic behavior, hallucinations and delusions. Until now, most scientists believed that it was likely that a cluster of relatively common genetic mutations was to blame.

Neural coding: The power of one

Nature Reviews Neuroscience 9, 78. February 2008

A single action potential in a single neuron can induce a behavioral response.

Conventional wisdom holds that the brain analyses patterns of activity in multiple cortical neurons in order to interpret incoming stimuli; however, the question of how many neurons must be active in order to generate a perception has remained unresolved. Two new studies indicate that the neural code that underlies sensory perceptions might be sparser than previously estimated and that activity in single neurons can contribute significantly to behavioural responses.

Synaptic plasticity: Learning through continuing potentiation

in Nature Reviews Neuroscience 9, 82 – 83. February 2008

Extended periods of synaptic plasticity involve activation of both NMDA and metabotropic glutamate receptors.

One of the main cellular mechanisms assumed to underlie learning is long-term potentiation (LTP), an experimental form of synaptic plasticity that results in a long-lasting increase in the strength of synaptic transmission. However, prolonged synaptic stimulation in vitro eventually stops producing further LTP (also known as ‘LTP occlusion’). So, how does ongoing experience result in further learning? Clem et al. now show that the opposing actions of activated N-methyl-D-aspartate receptors (NMDARs) and metabotropic glutamate receptors (mGluRs) allow progessive synaptic strengthening during sensory-induced plasticity.– Leonie Welberg

An actual and full review about synaptic plasticity can be found in the book Synaptic Plasticity: Molecular, Cellular, and Functional Aspects by Richard F. Thompson

An argument for an olfactory thalamus

Leslie M. Kay1, and S. Murray Sherman
Trends in Neurosciences
Volume 30, Issue 2, February 2007, Pages 47-53

Abstract
The mammalian olfactory system is unique in that sensory receptors synapse directly into the olfactory bulb of the forebrain without the thalamic relay that is common to all other sensory pathways. We argue that the olfactory bulb has an equivalent role to the thalamus, because the two regions have very similar structures and functions. Both the thalamus and the olfactory bulb are the final stage in sensory processing before reaching target cortical regions, at which there is a massive increase in neuron and synapse numbers. Thus, both structures act as a bottleneck that is a target for various modulatory inputs, and this arrangement enables efficient control of information flow before cortical processing occurs.

Development: The origins of interneuron diversity

Nature Reviews Neuroscience 8, 655 (September 2007)

An interneuron’s birth date may determine its molecular and physiological phenotype.

The enormous diversity of cortical interneuron subtypes presents a challenge for our understanding of their functional roles. A study by Fishell and colleagues examines the origins of interneuron diversity during development, highlighting the importance of an interneuron’s birth order in establishing its physiological properties…

Link to the full review.

Cell bodies get the shaft

Neuroscience Gateway. February 2008

Researchers physically separate neuron cell bodies and neurites to determine signaling pathways important in process extension.

What does it take for one neuron to reach out and touch another? In neuritogenesis, neurons develop the long, thin projections that eventually become axons and dendrites. Because these neurites are so small, it has been difficult to differentiate them biochemically from neuron cell bodies. Now Pertz et al. report proteomic analysis of separate populations of neurites and somas in a recent article in Proceedings of the National Academy of Sciences…

Link to the full review.

Grid cells

A grid cell is a type of neuron found in the entorhinal cortex (EC) that fires strongly when an animal is in specific locations in an environment. Grid cells were discovered in 2005 and it is hypothesized that a network of these cells constitute a mental map of the spatial environment (Hafting et al., 2005).
A good introduction to the concept of grid cells can be found in Phineas Cage Fun Club

Large-scale thalamocortical model

While the Blue Brain folk want to construct an incredibly detailed model of a single cortical column, a recent paper by Izhikevich and Edelman (Large-scale model of mammalian thalamocortical systems) reports on a less detailed model of the entire human thalamocortical system.

Some of the details of their model (roughly from large-scale to lower scale) include:
1. The cortical sheet’s geometry was constructed from human MRI data.
2. Projections among cortical regions were modeled using data from diffusion tensor MRI of the human brain (above image is Figure 1 of the paper showing a subset of such connections).
3. Synaptic connectivity patterns among neurons within and between cortical layers are based on detailed studies of cat visual cortex (and iterated to all of cortex).
4. Individual neurons are not modelled using the relatively computationally intensive Hodgkin-Huxely models, but a species of integrate-and-fire neuron that included a variable threshold, short-term synaptic plasticity, and long term spike-timing dependent plasticity.
5. The only subcortical structure included in the model is the thalamus, but the model does include simple simulated neuromodulatory influences (dopamine, acetylcholine).

Link to the full post BY ERIC THOMSON IN NEUROCHANNELS BLOG AT 2/25/2008 03:20:00 PM