Recent publications


Rethinking the Pedunculopontine Nucleus: From Cellular Organization to Function.

Mena-Segovia J. and Bolam J.P.

Neuron (2017) 94 (1): 7-18.

In this review we put together classical concepts and new evidence that dissects the influence of its different neuronal subtypes on their various targets, and we propose that the cholinergic neurons of the PPN have a central role in updating the behavioral state as a result of changes in environmental contingencies. Such a function is accomplished by a combined mechanism that simultaneously restrains ongoing obsolete actions while it facilitates new contextual associations.

Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits.

Dautan D., Souza A.S., Huerta-Ocampo I., Valencia M., Assous M., Witten I.B., Deisseroth K., Tepper J.M., Bolam J.P., Gerdjikov T.V. and Mena-Segovia J.

Nature Neuroscience (2016) 19 (8):1025-33.

We show how dopamine neurons operate in the context of cholinergic transmission and find that the afferents originating from two functionally distinct (motor and limbic) cholinergic nuclei of the brainstem selectively modulate subsets of neurons in the ventral tegmental area.


Structural and Functional Considerations of the Cholinergic Brainstem.

Mena-Segovia J.

J Neural Transm (Vienna) (2016) 123(7): 731-6.

In this review, some of the traditional ideas about the cholinergic brainstem are challenged in light of new evidence, suggesting that the intrinsic functional organization of the PPN and LDT is closely correlated with its connectivity with midbrain and forebrain circuits, and that the dynamics of cholinergic neuron signaling will give important clues for their role in behavior.


Extrinsic Sources of of Cholinergic Innervation of the Striatal Complex: A Whole-Brain Mapping Analysis.

Dautan D, Hacioğlu Bay H, Bolam JP, Gerdjikov TV and Mena-Segovia J.

Frontiers in Neuroanatomy (2016) 10:1.

After our publication in 2014 of the existence of an extrinsic source of acetylcholine to the striatum originated in the brainstem, it raised questions on whether other sources of acetylcholine may have passed unrecognized in the same way. In order to provide a solid and definite answer to these questions, we used conditional tracing in all brain cholinergic cell groups in ChAT::Cre rats and mapped cholinergic axons across the brain. Our results show that brainstem cholinergic axons (PPN and LDT) provide the only extrinsic cholinergic innervation to the striatal complex.


Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms.

Petzold A., Valencia M., Pal B. and Mena-Segovia J.

Frontiers in Neural Circuits (2015) 9:68. 

In this paper we demonstrate that cholinergic neurons of the PPN discharge phasically during brain state transitions, in contrast to putative glutamatergic neurons that discharge tonically and are likely to show a sustained high firing rate during the waking state. 


Previous publications (Oxford)

Dautan D., Huerta-Ocampo I., Witten I., Deisseroth K., Bolam J.P., Gerdjikov T. and Mena-Segovia J. A major external source of cholinergic innervation of the striatum and nucleus accumbens originates in the brainstem. Journal of Neuroscience (2014) 34: 4509-4518.

Valencia M., Chavez M., Artieda J., Bolam J.P. and Mena-Segovia J. Abnormal functional connectivity between motor cortex and pedunculopontine nucleus following chronic dopamine depletion. Journal of Neurophysiology (2014) 111: 434-40.

Huerta-Ocampo I., Mena-Segovia J. and Bolam J.P. Convergence of cortical and thalamic input to direct and indirect pathway medium spiny neurons in the striatum. Brain Structure and Function (2014). 219: 1787-1800. 

Martinez-Gonzalez C., van Andel J., Bolam J.P. and Mena-Segovia J. Divergent motor projections from the pedunculopontine nucleus are differentially regulated in Parkinsonism. Brain Structure and Function (2014). 219: 1451-1462. 

Valencia M., Artieda J., Bolam J.P. and Mena-Segovia J. Dynamic interaction of spindle and gamma activity during cortical slow oscillations and its modulation by subcortical inputs. PLoS One (2013) 8: 1-13. 

Martinez-Gonzalez C., Wang H.L., Micklem B.R., Bolam J.P. and Mena-Segovia J. Subpopulations of cholinergic, GABAergic and glutamatergic neurons in the pedunculopontine nucleus contain calcium-binding proteins and are heterogeneously distributed. European Journal of Neuroscience (2012) 35: 723-734.

Mena-Segovia J. and Bolam J.P. Phasic modulation of cortical high-frequency oscillations by pedunculopontine neurons. Progress in Brain Research (2011). 193: 85-92.

Martinez-Gonzalez C., Bolam J.P. and Mena-Segovia J. Topographical organization of the pedunculopontine nucleus. Frontiers in Neuroanatomy (2011) 5: 22.

os H., Magill P.J., Moss J., Bolam J.P. and Mena-Segovia J. Distinct types of non-cholinergic pedunculopontine neurons are differentially modulated during global brain states. Neuroscience (2010) 170: 78-91.

Mena-Segovia J., Micklem B.R., Nair-Roberts R., Ungless M.A. and Bolam J.P. GABAergic neuron distribution in the pedunculopontine nucleus define functional subterritories. Journal of Comparative Neurology (2009) 515: 397-408. 

Mena-Segovia J., Sims H.M., Magill P.J. and Bolam J.P. Cholinergic brainstem neurons modulate cortical gamma activity during slow oscillations. Journal of Physiology (2008) 586: 2947-60.

Obeso J.A., Marin C., Rodriguez-Oroz M.C., Blesa F.J., Benitez-Temiño B., Mena-Segovia J., Rodríguez M., Olanow C.W. The Basal Ganglia in Parkinson’s Disease: Current Concepts and Unexplained Observations. Annals of Neurology (2008), 64 Suppl. 2: S30-46.

Mena-Segovia J., Winn P. and Bolam J.P. Cholinergic modulation of midbrain dopaminergic systems. Brain Research Reviews (2008) 58: 265-71.

Mena-Segovia J., Bolam J.P. and Magill P.J. Pedunculopontine nucleus and basal ganglia: Distant relatives or part of the same family? Trends in Neurosciences (2004) 27: 585-588.

Mena-Segovia J., Favila R. and Giordano M. Long-term effects of striatal lesions on c-Fos immunoreactivity in the pedunculopontine nucleus. European Journal of Neuroscience (2004) 20: 2367-2376.

Mena-Segovia J. and Giordano M. Striatal dopaminergic stimulation produces c-Fos expression in the PPT and an increase in wakefulness. Brain Research (2003) 986: 30-38.

Vargas-Pérez H., Mena-Segovia J., Giordano M. and Díaz J.L. Induction of c-Fos in nucleus accumbens in naïve male Balb/C mice after wheel running. Neuroscience Letters (2003) 352: 81-84.

Mena-Segovia J., Cintra L., Prospéro-García O. and M. Giordano. Changes in the sleep-wake cycle after a striatal excitotoxic lesion. Behavioral Brain Research (2002) 136: 475-481.