Recent years have seen the application of increasingly powerful transgenic, optogenetic,
and chemogenetic methodologies in rodents. Armed with these tools, many studies have
shown how perturbations of specific subregions of the rodent frontal cortex can elicit
circumscribed behavioral phenotypes that resemble key aspects of psychiatric disorders.
For example, the rodent frontal cortex can be broadly divided into motor, medial prefrontal
cortex (mPFC), and orbitofrontal cortex (OFC) divisions; the mPFC can be further subdivided
into prelimbic (PL), infralimbic (IL), and cingulate (Cg) cortices, while the OFC
comprises the medial orbital (MO) and ventral and lateral orbital (VOLO) cortices.
Recent studies have specifically linked changes in MO and VOLO activity to the expression
of repetitive grooming behavior, which may model aspects of obsessive-compulsive disorder
- Ahmari S.E.
- Spellman T.
- Douglass N.L.
- Kheirbek M.A.
- Simpson H.B.
- Deisseroth K.
- et al.
Repeated cortico-striatal stimulation generates persistent OCD-like behavior.
- Burguiere E.
- Monteiro P.
- Feng G.
- Graybiel A.M.
Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive
), while many other studies have linked subregions of the mPFC to aspects of social
behavior, cognitive flexibility, working memory, chronic pain, and anxiety. At the
same time, a plethora of human brain imaging studies have implicated frontal cortical
networks in a variety of neuropsychiatric disorders. Notably, the subcallosal cingulate
gyrus—which includes Brodmann area 25 (a25), parts of area 24 (a24), and area 32 (a32)—has
been a focus of attention since it was found that deep brain stimulation of this region
can alleviate treatment-resistant depression in some patients (
- Hamani C.
- Mayberg H.
- Stone S.
- Laxton A.
- Haber S.
- Lozano A.M.
The subcallosal cingulate gyrus in the context of major depression.
). Taken together, these and numerous other studies across humans, nonhuman primates
(NHPs), and rodents suggest that many psychiatric disorders may be reconceptualized
as disorders of brain networks within which prefrontal or orbitofrontal regions represent
key nodes. In this context, a central challenge is identifying homologies between
cortical regions in humans and animal models, so that insights obtained via the use
of cutting edge tools in animal models can be translated to those regions of the human
brain that have been directly implicated in psychiatric disease. And while many modern
neuroscientific tools can be most readily exploited in rodents, the rodent prefrontal
and orbitofrontal cortices are vastly underdeveloped compared to their human counterparts.
Therefore, NHPs represent a critical bridge that may facilitate the synthesis of findings
across rodent and human studies. However, achieving this synthesis has been challenging.
In particular, there are many possible ways to identify corresponding brain regions
across species [e.g., based on cytoarchitectonic features and corticocortical connectivity
The organization of networks within the orbital and medial prefrontal cortex of rats,
monkeys and humans.
) or patterns of neuronal activity and behavioral functions (
- Seamans J.K.
- Lapish C.C.
- Durstewitz D.
Comparing the prefrontal cortex of rats and primates: insights from electrophysiology.
)]. In addition, there is controversy about whether many regions of primate PFC have
rodent analogs at all (
Forward frontal fields: phylogeny and fundamental function.