Neuroanatomy: End

I finished up the last component of my neuroanatomy course today.

This was one of the more intense courses I've taken during my Ph.D, simply because we had two weeks to learn almost every aspect of neuroanatomy as was humanly possible. For some reason courses like this one seem to bring out my philosophical side; maybe it's because in this case it was such a graphic depiction of this blob in our heads that we so often take for granted.

It's amazing to see the brain in all of its glory. Slicing structures left, right, top, bottom, and sideways really gives you an idea of how complicated this hunk of wet machinery really is.

Dynamic Reorganization of striatal circuits during the acquisition and consolidation of a skill

• Authors: Yin, Mulcare, Hilario, Clouse, Holloway, Davis, Hansson, Movinger, Costa
• Summary: 
• Region- and pathway specific plasticity sculpts the circuits involved in the performance of the skill as it becomes automatized.
• Background: 
• Dorsomedial (associative; caudate in primates) striatum (DMS) receives input primarily from association cortices such as the prefrontal cortex (PFC). The dorsolateral (sensorimotor; putamen in primates) striatum (DLS) receives input from sensorimotor cortices is critical for the more gradual acquisition of habitual and automatic behavior.
• CPC: 
• What role does the cerebellum play, if any, in the process of "transferring" newly learned skills to some sort of storage? Is it too general to say that DMS is involved in learning causal relationships, whereas DLS is involved in automatic association of these causes and effects?
• Question(s): 
• Can changes in striatal neural activity observed during skill learning be mediated by synaptic plasticity or excitability chagnes in medium spiny projections neurons in the dorsal striatum using an ex vivo (a slice preparation) approach.
• Result(s): 
• "... task-related activity in these striatal regions differed during the acquisition and consolidation of a new skill, with the DMS being engaged during the early phase and the DLS being engaged during the late phase."
• "[in the ex vivo preparation, ] [l]earning was accompanied by long-lasting changes in glutamatergic transmission."
• "These changes evolved dynamically during the different phases of skill learning;
• "Changes in the DMS were predominant early in training, whereas changes in the DLS emerged only after extensive training."
• "Long-lasting changes in the DLS after extensive training were pathway specific and occurred predominantly in DA receptor 2 (D2)-expressing striatopalidal medium spiny neurons."
• Conclusion(s):
• "..., the performance of the skill after extended training became less dependent on the activation of D1-type DA receptors, which are mainly expressed in striatonigral neurons."
• Method(s):
• DMS/DLS Involvement in Early and Late Skill Learning
• Quantified the modulation of activity using the following equation
• In the DMS the rate modulation increased during the early phase of training but returned to naive levels with further training
• In the DLS, the modulation of firing rate increased gradually with training.
• Accompanied by a decrease in baseline firing rate during the intertrial period.
• The authors interpret this as an increase in signal-to-noise ratio after extended training.
• Next question:
• Are the region-specific changes observed in vivo driven by glutamatergic synaptic plasticity or excitability changes in the striatum by training the mice for either 1 day or 8 days on an accelerating rotarod?
• This was followed up by examining ex vivo the changes in DMS and DLS related to the different phases of skill learning.

Functional architecture of basal ganglia circuits: neural substrates of parallel processing

Authors: Garret E. Alexander, Michael D. Crutcher
Summary: This paper discusses the evidence for parallelization of circuitry within the individual circuits of the basal ganglia.

• Previous Views:
• The basal ganglia served to integrate converging influences from cortical association and sensorimotor areas during their passage through basal ganglia to common thalamic target zones.
• Same BG recipient zones in thalamus received ascending, convergent inputs from the cerebellum and returned their own projections exclusively to primary motor cortex.
• More Recent Evidence:
• BG and cerebellar projections are directed to completely separate target zones with the thalamus.
• Association and sensorimotor cortex form closed circuits between cortex, BG, and thalamus.
• Output projects not only to primary motor cortex, but to virtually the entire frontal lobe.
• Main Question: 
• Is a parallel functional architecture evident within individual basal ganglia circuits?
• Motor Circuit:
• Features Intrinsic to Parallel Organization
• Cortex $\rightarrow$ glutamatergic $\rightarrow$ striatum $==$ input
• Basal Ganglia $\rightarrow$ tonic, GABA-mediated inhibitory effect on nuclei in thalamus
• modulated by 2 opposing but parallel pathways that pass from striatum $\rightarrow$ basal ganglia output nuclei
• Direct pathway $\rightarrow$ output nuclei
• comes from inhibitory striatal efferents that contain GABA and substance P $\rightarrow \not$ thalamic stage
• Indirect pathway $\rightarrow$ GPe $\rightarrow$ subthalamic nucleus via GABAergic pathway $\rightarrow$ excitatory (Glu)
• GPe neurons exert a tonic inhibitory influence on the subthalamic nucleus.
• GABA/enk projection from striatum suppress activity of GPe neurons $\rightarrow$ disinhibits the subthalamic nucleus $\rightarrow$ excitatory drive on the output nuclei $\rightarrow$ increases inhibition of their efferent targets within the thalamus.

Neuroanatomy: Day 0

I'm taking an intensive 2-week neuroanatomy course at NYU for the next two weeks. I'll be posting notes and interesting tidbits about things that I'm learning. This post will be on the topic(s) of the first 3 chapters of our textbook.

Neurodevelopment happens to be something that I'm particularly weak on, and the first chapter of our text jumps right into it, for better or for worse.

A section titled: "A note on times and ages" is in part this inspiration for this post. This section points out some very basic clinical conventions used to delimit certain periods of neural development:

1. Pregnancy is timed from the 1st day of the last menstrual period.

2. An 8-week old ball of cells is called a fetus.

3. The embryonic period is divided in to 23 Carnegie stages (not sure where Carnegie comes from), with the neural folds appearing at stage 8.

More on development:

By the end of the 3rd week the neural folds have begun to fuse with one another to form the neural tube. The cells that line the tube will eventually become the neurons that make up all of the neurons in the CNS.

Neural crests are what give rise to many neuroglia and other cells outside of the nervous system. These cells migrate extensively. 

An interesting fact of the brain is that during development there are many more neurons formed than will go on to exist when the animal is an adult. Evidence has shown that in vertebrates cells that died were those that failed to make synaptic connections. Unfortunately, there is currently no evidence to suggest that adult human brains regenerate neurons (with the exception of an area of the hippocampus and olfactory neurons).

The developing nervous system is conventionally divided into 5 parts and their names change as the organism develops:

1. Telencephalon $\rightarrow$ Cortex
2. Diencephalon $\rightarrow$ Thalamus/Hypothalamus
3. Mesencephalon $\rightarrow$ Midbrain
4. Metencephalon $\rightarrow$ Pons and Cerebellum
5. Myelencephalon $\rightarrow$ Medulla Oblongata

Here's a nice breakdown from the text:

Another interesting part of neural development is the construction of the meninges. The meninges are a membraneous tissue that protect the brain. The meninges is somewhat like plastic wrap for the brain, at least upon initial visual inspection.

Key parts of the brain:

• Spinal cord
• Least differentiated part of the nervous system
• pair of nerves is connected to the spinal cord (dorsal sensory root, ventral motor root)
• H-shaped spatial organization with gray matter as the H and white matter in the surrounding area
• Gray matter in the spinal cord is important for reflexes
• Medulla oblongata
• A continuation of the spinal cord
• Pons
• Two-part structure
• Tegmentum
• ascending/descending tracts
• Basal pons
• Provides connections between the cortex of a cerebral hemisphere and that of the contralateral cerebellar hemisphere
• Midbrain
• Dorsal region
• Tectum: lower level visual/auditory control
• Red nucleus/substantia nigra: important in motor control
• attached to the mid brain via the superior cerebellar peduncles
• Cerebellum
• Extremely large, contains most of the neurons of the brain
• Important for muscular compensation during movement
• Diencephalon
• Central core of the cerebrum
• Largest component is the thalamus
• Epithalamus and pineal gland constitute an endocrine organ
• Interestingly, the retina is a derivative of the diencephalon
• Telencephalon

A human brain (!) :