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Background: Prefrontal cortex (PFC) represents the highest level of integration and control of psychic and behavioral states. Several dysfunctions such as autism, hyperactivity disorders, depression, and schizophrenia have been related with alterations in the prefrontal cortex (PFC). Among the cortical layers of the PFC, layer II shows a particular vertical pattern of organization, the highest cell density and the biggest non-pyramidal/pyramidal neuronal ratio. We currently characterized the layer II cytoarchitecture in human areas 10, 24, and 46.

Objective: We focused particularly on the inhibitory neurons taking into account that these cells are involved in sustained firing (SF) after stimuli disappearance.

Methods: Postmortem samples from five subjects who died by causes different to central nervous system diseases were studied. Immunohistochemistry for the neuronal markers, NeuN, parvalbumin, calbindin, and calretinin were used. NeuN targeted the total neuronal population while the rest of the markers specifically the interneurons.

Results: Cell density and soma size were statically different between areas 10, 46, 24 when using NeuN. Layer II of area 46 showed the highest cell density. Regarding interneurons, PV+-cells of area 46 showed the highest density and size, in accordance to the proposal of a dual origin of the cerebral cortex. Interhemispheric asymmetries were not identified between homologue areas.

Conclusion: First, our findings suggest that layer II of area 46 exhibits the most powerful inhibitory system compared to the other prefrontal areas analyzed. This feature is not only characteristic of the PFC but also supports a particular role of layer II of area 46 in SF. Additionally, known functional asymmetries between hemispheres might not be supported by morphological asymmetries.


Gabriel Arteaga, Centro de Estudios Cerebrales, Facultad de Salud, Universidad del Valle cerebrales

Biologo, PhD en neurociencias escuela de ciencias basicas universidad del valle. Director Instituto de Psicologia.

Efrain Buritica, Centro de Estudios Cerebrales, Facultad de Salud, Universidad del Valle

Psicólogo, magister en morfología Universidad del Valle. Profesor asistente. Jefe departamento de morfología

Hernan Pimienta, Centro de Estudios Cerebrales Facultad de Salud Universidad del Valle

Biologo, magister en morfologia universidad del Valle. Fellow en neurociencias Universidad de Harvard. Profesor Titular catedra neuroanatomia. Profesor distinguido. Maestro Universitario. Premio a toda una vida otorgado por el Colegio colombiano de neurociencias. Ex vicedecano de investigaciones.
Arteaga, G., Buritica, E., Escobar, M. I., & Pimienta, H. (2024). Human prefrontal layer II interneurons in areas 46, 10 and 24. Colombia Medica, 46(1), 19–25. (Original work published March 30, 2015)

Yeterian E, Pandya D, Tomaiuolo F, Petrides M. The cortical connectivity of the prefrontal cortex in the monkey brain. Cortex. 2012; 48(1): 58–81.

Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011; 306(18): 2001–10.

Casanova MF. The neuropathology of autism. Brain Pathol. 2007; 17(4): 422–33.

Oh DH, Son H, Hwang S, Kim SH. Neuropathological abnormalities of astrocytes, GABAergic neurons, and pyramidal neurons in the dorsolateral prefrontal cortices of patients with major depressive disorder. Eur Neuropsychopharmacol. 2012; 22(5): 330–8.

Halperin J, Schulz K. Revisiting the role of the prefrontal cortex in the pathophysiology of attention-deficit/hyperactivity disorder. Psychol Bull. 2006; 132(4): 560–81.

Gonzalez-Burgos G, Fish KN, Lewis DA. GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia. Neural Plast. 2011; 2011: 723184.

Glausier J, Lewis D. Selective pyramidal cell reduction of GABA(A) receptor a1 subunit messenger RNA expression in schizophrenia. Neuropsychopharmacology. 2011; 36(10): 2103–10.

Zaitsev A, Povysheva N, Gonzalez-Burgos G, Rotaru1 D, Fish KN, Krimer LS, et al. Interneuron diversity in layers 2-3 of monkey prefrontal cortex. Cereb cortex. 2009; 19(7): 1597–615.

Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci. 2005; 6(4): 312–24.

Ichinohe N. Small-scale module of the rat granular retrosplenial cortex: an example of the minicolumn-like structure of the cerebral cortex. Front Neuroanat. 2012; 5: 69.

Ichinohe N, Hyde J, Matsushita A, Ohta K, Rockland K. Confocal mapping of cortical inputs onto identified pyramidal neurons. Front Biosci. 2008; 13: 6354–73.

Ichinohe N, Fujiyama F, Kaneko T, Rockland KS. Honeycomb-like mosaic at the border of layers 1 and 2 in the cerebral cortex. J Neurosci. 2003; 23(4): 1372–82.

Escobar M, Pimienta H, Caviness V, Jacobson M, Crandall J, Kosik K. Architecture of apical dendrites in the murine neocortex: dual apical dendritic systems. Neuroscience. 1986; 17(4): 975–89.

Wang X-J Neurophysiological and computational principles of cortical rhythms in cognition. Physiol Rev. 2010; 90(3): 1195–268.

Compte A. Computational and in vitro studies of persistent activity: edging towards cellular and synaptic mechanisms of working memory. Neuroscience. 2006; 139(1): 135–51.

Lara AH, Wallis JD. Executive control processes underlying multi-item working memory. Nat Neurosci. 2014; 17(6): 876–83.

Lewis DA, González-Burgos G. Neuroplasticity of neocortical circuits in schizophrenia. Neuropsychopharmacology. 2008; 33(1): 141–65.

Elston G, Benavides-Piccione R, Elston A, Manger P, Defelipe J. Pyramidal cells in prefrontal cortex of primates: marked differences in neuronal structure among species. Front Neuroanat. 2011; 5: 2.

Dombrowski SM, Hilgetag CC, Barbas H. Quantitative architecture distinguishes prefrontal cortical systems in the rhesus monkey. Cereb Cortex. 2001; 11(10): 975–88.

Barbas H. Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices. Brain Res Bull. 2000; 52(5): 319–30.

Condé F, Lund J, Jacobowitz D, Baimbridge K, Lewis D. Local circuit neurons immunoreactive for calretinin, calbindin D-28k or parvalbumin in monkey prefrontal cortex: distribution and morphology. J Comp Neurol. 1994; 341(1): 95–116.

Raghanti M, Spocter M, Butti C, Hof P, Sherwood C. A comparative perspective on minicolumns and inhibitory GABAergic interneurons in the neocortex. Front Neuroanat. 2010; 4: 3.

Druga R. Neocortical inhibitory system. Folia Biol (Praha) 2009; 55(6): 201–17.

DeFelipe J, Ballesteros-Yáñez I, Inda M, Muñoz A. Double-bouquet cells in the monkey and human cerebral cortex with special reference to areas 17 and 18. Prog Brain Res. 2006; 154: 15–32.

Caputi A, Rozov A, Blatow M, Monyer H. Two calretinin-positive GABAergic cell types in layer 2/3 of the mouse neocortex provide different forms of inhibition. Cereb Cortex. 2009; 19(6): 1345–59.

Melchitzky D, Eggan S, Lewis D. Synaptic targets of calretinin-containing axon terminals in macaque monkey prefrontal cortex. Neuroscience. 2005; 130(1): 185–95.

Inan M, Blázquez-Llorca L, Merchán-Pérez A, Anderson S, DeFelipe J, Yuste R. Dense and overlapping innervation of pyramidal neurons by chandelier cells. J Neurosci. 2013; 33(5): 1907–14.

Gonzalez-Burgos G, Lewis D. GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia. Schizophr Bull. 2008; 34(5): 944–61.

Woodruff AR, Anderson SA, Yuste R. The enigmatic function of chandelier cells. Front Neurosci. 2010; 4: 201.

Kaller CP, Loosli SV, Rahm B, Gössel A, Schieting S, Hornig T, et al. Working memory in schizophrenia: behavioral and neural evidence for reduced susceptibility to item-specific proactive interference. Biol Psychiatry. 2014; 76(6): 486–94.

Eich T, Nee D, Insel C, Malapani C, Smith E. Neural correlates of impaired cognitive control over working memory in schizophrenia. Biol Psychiatry. 2014; 76(2): 146–53.

Arnsten A, Wang M, Paspalas C. Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses. Neuron. 2012; 76(1): 223–39.

Melchitzky DS, Lewis DA. Dendritic-targeting GABA neurons in monkey prefrontal cortex: comparison of somatostatin- and calretinin-immunoreactive axon terminals. Synapse. 2008; 62(6): 456–65.

Lewis D, Melchitzky D, Gonzales-Burgos G. Specificity in the functional architecture of primate prefrontal cortex. J Neurocytol. 2002; 31(3-5): 265–76.

Opris I, Fuqua J, Huettl P, Gerhardt GA, Berger TW, Hampson RE, et al. Closing the loop in primate prefrontal cortex: inter-laminar processing. Front Neural Circuits. 2012; 6: 88.

Opris I, Hampson R, Gerhardt G, Berger T, Deadwyler S. Columnar processing in primate pFC: evidence for executive control microcircuits. J Cogn Neurosci. 2012; 24(12): 2334–47.

Opris I, Santos L, Gerhardt GA, Song D, Berger TW, Robert E. et al. Prefrontal cortical microcircuits bind perception to executive control. Sci Rep. 2013; 3: 2285.

Opris I, Casanova M. Prefrontal cortical minicolumn: from executive control to disrupted cognitive processing. Brain. 2014;137(7):1863–1875.


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Received 2014-08-21
Accepted 2015-02-02
Published 2024-06-17