Synaptogenesis in the Prefrontal Cortex of Rhesus Monkeys

The advent of new technology has led to a proliferation of studies examining the functional roles of discrete prefrontal cortical areas. This has created a need for more precise information regarding the morphological characteristics of this region. Existing architectonic maps of human and monkey brains are not compatible with regard to areal delineations and topography, creating significant difficulty in interpreting comparative data. Therefore, we have re-examined the comparative morphological organization of the prefrontal cortex in humans and rhesus monkeys. Our analysis indicates that the architectonic areas in both species correspond in terms of morphological features as well as topographical locations. We have developed a common organizational schema for these areas, thereby allowing for a resolution of previous discrepancies. Moreover, in monkeys a connectional analysis has revealed that each of the newly designated areas is characterized by a unique pattern of cortical relationships. The present organizational schema provides a framework for interrelating findings such as those obtained from human brain imaging studies with those from behavioural investigations of non-human primates.

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Synaptic Estrogen Receptor- Levels in Prefrontal Cortex in Female Rhesus Monkeys and Their Correlation with Cognitive Performance

Journal of Neuroscience ◽

10.1523/jneurosci.3192-10.2010 ◽

2010 ◽

Vol 30 (38) ◽

pp. 12770-12776 ◽

Cited By ~ 63

Author(s):

A. C. J. Wang ◽

Y. Hara ◽

W. G. M. Janssen ◽

P. R. Rapp ◽

J. H. Morrison

Keyword(s):

Estrogen Receptor ◽

Prefrontal Cortex ◽

Cognitive Performance ◽

Rhesus Monkeys ◽

Female Rhesus

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Free behavior of rhesus monkeys following lesions of the dorsolateral and orbital prefrontal cortex in infancy

Experimental Brain Research ◽

10.1007/bf00237919 ◽

1971 ◽

Vol 12 (3) ◽

Cited By ~ 26

Author(s):

DouglasM. Bowden ◽

PatriciaS. Goldman ◽

H.Enger Rosvold ◽

RichardL. Greenstreet

Keyword(s):

Prefrontal Cortex ◽

Rhesus Monkeys ◽

Orbital Prefrontal Cortex ◽

Free Behavior

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Plaques in prefrontal cortex of aged, behaviorally-tested rhesus monkeys: Incidence, distribution, and relationship to task performance

Neurobiology of Aging ◽

10.1016/0197-4580(93)90068-m ◽

1993 ◽

Vol 14 (6) ◽

pp. 675-676 ◽

Cited By ~ 15

Author(s):

Linda C. Cork

Keyword(s):

Prefrontal Cortex ◽

Task Performance ◽

Rhesus Monkeys

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Chemogenetic actuator drugs impair prefrontal cortex-dependent working memory in rhesus monkeys

10.1101/864140 ◽

2019 ◽

Author(s):

Nicholas A. Upright ◽

Mark G. Baxter

Keyword(s):

Working Memory ◽

Prefrontal Cortex ◽

Rhesus Monkeys ◽

Memory Performance ◽

Memory Function ◽

Muscarinic Acetylcholine Receptor ◽

Designer Drugs ◽

Delayed Response ◽

Response Task ◽

Delayed Response Task

AbstractThe most common chemogenetic neuromodulatory system, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is no longer sensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug. We investigated working memory performance after injections of three DREADD agonists, clozapine, olanzapine, and deschloroclozapine, in male rhesus monkeys tested in a spatial delayed response task. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from mean performance after vehicle in any of the four subjects. Administration of 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after administration of 0.1 mg/kg olanzapine and two monkeys were impaired after the 0.3 mg/kg dose of deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs to confirm that effects following DREADD receptor transduction are not due to the actuator drug itself, as well as validating the behavioral pharmacology of DREADD actuator drugs in the specific tasks under study.Significance StatementChemogenetic technologies, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), allow for precise and remote manipulation of neuronal circuits. In the present study, we tested monkeys in a spatial delayed response task after injections of three actuator drugs – clozapine, olanzapine, and deschloroclozapine. We found that monkeys showed significant working memory impairments after 0.2 mg/kg clozapine, 0.1 mg/kg olanzapine, and 0.3 mg/kg deschloroclozapine compared to vehicle performance. In monkeys that showed impairments, these deficits were particularly apparent at longer delay periods. It is imperative to validate the drugs and dosages in the particular behavioral test to ensure any behavior after DREADD transduction can be attributed to activation of the receptors and not administration of the actuator drug itself.

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