Septum and medial frontal cortex contribution to spatial problem-solving

Poucet, Bruno; Herrmann, Thom

doi:10.1016/0166-4328(90)90139-6

Cited by 53 publications

(22 citation statements)

References 34 publications

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“…The medial septal region (medial septum and diagonal band of Broca, MS/DB), which controls hippocampal excitability and synaptic plasticity associated to learning and memory (Olton et al, 1978; Poucet and Herrmann, 1990; Dutar et al, 1995; Niewiadomska et al, 2009), includes different neuronal subpopulations with heterogeneous morphology, biochemical, electrophysiological properties and connectivity. In fact, a detailed characterization of the in vivo septo-hippocampal projections has recently given strong evidence of three distinct neurotransmitter pathways including GABAergic (27.8%), cholinergic (47%) and glutamatergic (24.5%) neurons (Colom et al, 2005, 2013; Wu and Yeh, 2005; Huh et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Impaired NGF/TrkA Signaling Causes Early AD-Linked Presynaptic Dysfunction in Cholinergic Primary Neurons

Latina

Caioli

Zona

et al. 2017

Front. Cell. Neurosci.

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Alterations in NGF/TrkA signaling have been suggested to underlie the selective degeneration of the cholinergic basal forebrain neurons occurring in vivo in AD (Counts and Mufson, 2005; Mufson et al., 2008; Niewiadomska et al., 2011) and significant reduction of cognitive decline along with an improvement of cholinergic hypofunction have been found in phase I clinical trial in humans affected from mild AD following therapeutic NGF gene therapy (Tuszynski et al., 2005, 2015). Here, we show that the chronic (10–12 D.I.V.) in vitro treatment with NGF (100 ng/ml) under conditions of low supplementation (0.2%) with the culturing serum-substitute B27 selectively enriches the basal forebrain cholinergic neurons (+36.36%) at the expense of other non-cholinergic, mainly GABAergic (−38.45%) and glutamatergic (−56.25%), populations. By taking advantage of this newly-developed septo-hippocampal neuronal cultures, our biochemical and electrophysiological investigations demonstrate that the early failure in excitatory neurotransmission following NGF withdrawal is paralleled by concomitant and progressive loss in selected presynaptic and vesicles trafficking proteins including synapsin I, SNAP-25 and α-synuclein. This rapid presynaptic dysfunction: (i) precedes the commitment to cell death and is reversible in a time-dependent manner, being suppressed by de novo external administration of NGF within 6 hr from its initial withdrawal; (ii) is specific because it is not accompanied by contextual changes in expression levels of non-synaptic proteins from other subcellular compartments; (ii) is not secondary to axonal degeneration because it is insensible to pharmacological treatment with known microtubule-stabilizing drug such paclitaxel; (iv) involves TrkA-dependent mechanisms because the effects of NGF reapplication are blocked by acute exposure to specific and cell-permeable inhibitor of its high-affinity receptor. Taken together, this study may have important clinical implications in the field of AD neurodegeneration because it: (i) provides new insights on the earliest molecular mechanisms underlying the loss of synaptic/trafficking proteins and, then, of synapes integrity which occurs in vulnerable basal forebrain population at preclinical stages of neuropathology; (ii) offers prime presynaptic-based molecular target to extend the therapeutic time-window of NGF action in the strategy of improving its neuroprotective in vivo intervention in affected patients.

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Section: Resultsmentioning

confidence: 99%

Impaired NGF/TrkA Signaling Causes Early AD-Linked Presynaptic Dysfunction in Cholinergic Primary Neurons

Latina

Caioli

Zona

et al. 2017

Front. Cell. Neurosci.

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“…Compared to the caudal DRN, the rostral DRN projects more densely to virtually all neocortical regions (Vertes, 2004), which are regarded as the most recently evolved brain regions and are thought to be important for processing higher cognitive functions in mammals, such as spatial reasoning. Specifically, the frontal cortex may be an important region regulating spatial abilities in rodents and humans (Poucet, 1990; Poucet and Herrmann, 1990; Miotto et al, 1996; Bimonte-Nelson et al, 2003a). Therefore, activation of 5-HT activity from the rostral DRN may modulate cognitive performance in the DMS task via altering the cortical activity in regions such as the frontal cortex.…”

Section: Discussionmentioning

confidence: 99%

Benefits of Hormone Therapy Estrogens Depend on Estrogen Type: 17β-Estradiol and Conjugated Equine Estrogens Have Differential Effects on Cognitive, Anxiety-Like, and Depressive-Like Behaviors and Increase Tryptophan Hydroxylase-2 mRNA Levels in Dorsal Raphe Nucleus Subregions

et al. 2016

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Decreased serotonin (5-HT) function is associated with numerous cognitive and affective disorders. Women are more vulnerable to these disorders and have a lower rate of 5-HT synthesis than men. Serotonergic neurons in the dorsal raphe nucleus (DRN) are a major source of 5-HT in the forebrain and play a critical role in regulation of stress-related disorders. In particular, polymorphisms of tryptophan hydroxylase-2 (TpH2, the brain-specific, rate-limiting enzyme for 5-HT biosynthesis) are implicated in cognitive and affective disorders. Administration of 17β-estradiol (E2), the most potent naturally circulating estrogen in women and rats, can have beneficial effects on cognitive, anxiety-like, and depressive-like behaviors. Moreover, E2 increases TpH2 mRNA in specific subregions of the DRN. Although conjugated equine estrogens (CEE) are a commonly prescribed estrogen component of hormone therapy in menopausal women, there is a marked gap in knowledge regarding how CEE affects these behaviors and the brain 5-HT system. Therefore, we compared the effects of CEE and E2 treatments on behavior and TpH2 mRNA. Female Sprague-Dawley rats were ovariectomized, administered either vehicle, CEE, or E2 and tested on a battery of cognitive, anxiety-like, and depressive-like behaviors. The brains of these animals were subsequently analyzed for TpH2 mRNA. Both CEE and E2 exerted beneficial behavioral effects, although efficacy depended on the distinct behavior and for cognition, on the task difficulty. Compared to CEE, E2 generally had more robust anxiolytic and antidepressant effects. E2 increased TpH2 mRNA in the caudal and mid DRN, corroborating previous findings. However, CEE increased TpH2 mRNA in the caudal and rostral, but not the mid, DRN, suggesting that distinct estrogens can have subregion-specific effects on TpH2 gene expression. We also found differential correlations between the level of TpH2 mRNA in specific DRN subregions and behavior, depending on the type of behavior. These distinct associations imply that cognition, anxiety-like, and depressive-like behaviors are modulated by unique serotonergic neurocircuitry, opening the possibility of novel avenues of targeted treatment for different types of cognitive and affective disorders.

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“…The septohippocampal system has been implicated in learning and memory (Olton et al, 1978;Poucet and Herrmann, 1990;Dutar et al, 1995). Within this system, the cholinergic and GABAergic components have been subject to considerable experimental attention, having been demonstrated in previous studies to contribute prominently to learning and mnemonic functions (Deutsch and Rocklin, 1967;Chrobak and Napier, 1992;BergerSweeney et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Nerve Growth Factor Rapidly Increases Muscarinic Tone in Mouse Medial Septum/Diagonal Band of Broca

Yeh²

2005

J. Neurosci.

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Nerve growth factor (NGF) has been implicated in maintaining and regulating normal functioning of the septohippocampal pathway. However, many aspects of its physiological actions and the underlying mechanisms await elucidation. In this study, we investigated the effect of acute NGF exposure on neurons in the mouse medial septum/diagonal band of Broca (MS/DB), focusing on the cholinergic neurons and the subpopulation of noncholinergic neurons that were identified to be putatively GABAergic. We report that MS/DB neurons in a thin slice preparation, when exposed to NGF via bath perfusion, rapidly and indiscriminately increased the rate of spontaneous firing in all MS/DB neurons. However, focal application of NGF to individual MS/DB neurons increased spontaneous firing in cholinergic, but not in the noncholinergic, subpopulation. The NGF-induced effect on cholinergic neurons was direct, requiring activation and signaling via TrkA receptors, which were immunohistochemically localized to the cholinergic neurons in the MS/DB. TrkA receptors were absent in putative GABAergic MS/DB neurons, and blockade of TrkA signaling in these and other noncholinergic neurons had no effect on their firing activity after exposure to NGF. Conversely, methyl scopolamine, blocked the increased firing activity of noncholinergic neurons during bath perfusion of NGF. We propose a cell type-specific mode of action for NGF in the MS/DB. The neurotrophin directly enhances cholinergic neuronal activity in the MS/DB through TrkA-mediated signaling, increasing acetylcholine release and, thus, muscarinic tone. This increase in muscarinic tone, in turn, results in heightened firing activity in noncholinergic MS/DB neurons.

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Septum and medial frontal cortex contribution to spatial problem-solving

Cited by 53 publications

References 34 publications

Impaired NGF/TrkA Signaling Causes Early AD-Linked Presynaptic Dysfunction in Cholinergic Primary Neurons

Impaired NGF/TrkA Signaling Causes Early AD-Linked Presynaptic Dysfunction in Cholinergic Primary Neurons

Benefits of Hormone Therapy Estrogens Depend on Estrogen Type: 17β-Estradiol and Conjugated Equine Estrogens Have Differential Effects on Cognitive, Anxiety-Like, and Depressive-Like Behaviors and Increase Tryptophan Hydroxylase-2 mRNA Levels in Dorsal Raphe Nucleus Subregions

Nerve Growth Factor Rapidly Increases Muscarinic Tone in Mouse Medial Septum/Diagonal Band of Broca

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