scholarly journals Basal forebrain gating by somatostatin neurons drives cortical activity

2017 ◽  
Author(s):  
Nelson Espinosa ◽  
Alejandra Alonso ◽  
Cristian Morales ◽  
Pablo Fuentealba

AbstractThe basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing cells constitute a local GABAergic source known to functionally inhibit the major cortically-projecting cell types. However, it remains unclear if somatostatin cells can regulate the basal forebrain’s synaptic output and thus control cortical dynamics. Here, we demonstrate in mice that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo increased spiking of some basal forebrain cells, rapidly enhancing and desynchronizing neural activity in the prefrontal cortex, inhibiting slow rhythms and increasing gamma oscillations. Locomotor activity was specifically increased in quiescent animals, but not in active mice. Altogether, we provide physiological and behavioral evidence indicating that somatostatin cells are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms.

2006 ◽  
Vol 96 (6) ◽  
pp. 3209-3219 ◽  
Author(s):  
Shih-Chieh Lin ◽  
Damien Gervasoni ◽  
Miguel A. L. Nicolelis

Traditionally, most basal forebrain (BF) functions have been attributed to its cholinergic neurons. However, the majority of cortical-projecting BF neurons are noncholinergic and their in vivo functions remain unclear. We investigated how BF modulates cortical dynamics by simultaneously recording ≤50 BF single neurons along with local field potentials (LFPs) from the prefrontal cortex (PFCx) in different wake–sleep states of adult rats. Using stereotypical spike time correlations, we identified a large (roughly 70%) subset of BF neurons, which we named BF tonic neurons (BFTNs). BFTNs fired tonically at 2–8 Hz without significantly changing their average firing rate across wake–sleep states. As such, these cannot be classified as cholinergic neurons. BFTNs substantially increased the spiking variability during waking and rapid-eye-movement sleep, by exhibiting frequent spike bursts with <50-ms interspike interval. Spike bursts among BFTNs were highly correlated, leading to transient population synchronization events of BFTN ensembles that lasted on average 160 ms. Most importantly, BFTN synchronization occurred preferentially just before the troughs of PFCx LFP oscillations, which reflect increased cortical activity. Furthermore, BFTN synchronization was accompanied by transient increases in prefrontal cortex gamma oscillations. These results suggest that synchronization of BFTN ensembles, which are likely to be formed by cortical-projecting GABAergic neurons from the BF, could be primarily responsible for fast cortical modulations to provide transient amplification of cortical activity.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1208 ◽  
Author(s):  
Michael J. Garabedian ◽  
Charles A. Harris ◽  
Freddy Jeanneteau

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.


2016 ◽  
Author(s):  
Detlef H. Heck ◽  
Samuel S. McAfee ◽  
Yu Liu ◽  
Abbas Babajani-Feremi ◽  
Roozbeh Rezaie ◽  
...  

SummaryThe brain generates oscillatory neuronal activity at a broad range of frequencies and the presence and amplitude of certain oscillations at specific times and in specific brain regions are highly correlated with states of arousal, sleep, and with a wide range of cognitive processes. The neuronal mechanisms underlying the generation of brain rhythms are poorly understood, particularly for low-frequency oscillations. We recently reported that respiration-locked olfactory bulb activity causes delta band (0.5-4 Hz) oscillatory neuronal activity in the whisker sensory (barrel) cortex in mice. Furthermore, gamma oscillations (30 – 100Hz), which are widely implicated in cognitive processing, were power-modulated in synchrony with the respiratory rhythm. These findings link afferent sensory activity caused by respiration directly to cortical rhythms associated with cognitive functions. Here we review the related literature and present new evidence to propose that respiration has a direct influence on oscillatory cortical activity, including gamma oscillations, and on transitions between synchronous and asynchronous cortical network states (marked by phase transitions). Oscillatory cortical activity, as well as phase transitions, has been implicated in cognitive functions, potentially linking respiratory phase to cognitive processing. We further argue that respiratory influence on cortical activity is present in most, and possibly in all areas of the neocortex in mice and humans. We furthermore suggest that respiration had a role in modulating cortical rhythms from early mammalian evolution. Early mammals relied strongly on their olfactory sense and had proportionately large olfactory bulbs. We propose that to this day the respiratory rhythm remains an integral element of dynamic cortical activity in mammals. We argue that breathing modulates all cortical functions, including cognitive and emotional processes, which could elucidate the well-documented but largely unexplained effects of respiratory exercises on mood and cognitive function.


2017 ◽  
Author(s):  
Bryan M. Krause ◽  
Caitlin A. Murphy ◽  
Daniel J. Uhlrich ◽  
Matthew I. Banks

AbstractSpatio-temporal cortical activity patterns relative to both peripheral input and local network activity carry information about stimulus identity and context. GABAergic interneurons are reported to regulate spiking at millisecond precision in response to sensory stimulation and during gamma oscillations; their role in regulating spike timing during induced network bursts is unclear. We investigated this issue in murine auditory thalamo-cortical (TC) brain slices, in which TC afferents induced network bursts similar to previous reports in vivo. Spike timing relative to TC afferent stimulation during bursts was poor in pyramidal cells and SOM+ interneurons. It was more precise in PV+ interneurons, consistent with their reported contribution to spiking precision in pyramidal cells. Optogenetic suppression of PV+ cells unexpectedly improved afferent-locked spike timing in pyramidal cells. In contrast, our evidence suggests that PV+ cells do regulate the spatio-temporal spike pattern of pyramidal cells during network bursts, whose organization is suited to ensemble coding of stimulus information. Simulations showed that suppressing PV+ cells reduces the capacity of pyramidal cell networks to produce discriminable spike patterns. By dissociating temporal precision with respect to a stimulus versus internal cortical activity, we identified a novel role for GABAergic cells in regulating information processing in cortical networks.


2018 ◽  
Author(s):  
Teemu Aitta-aho ◽  
Y Audrey Hay ◽  
Benjamin U. Phillips ◽  
Lisa M. Saksida ◽  
Tim J. Bussey ◽  
...  

SummaryThe central cholinergic system and the amygdala are important for motivation and mnemonic processes. Different cholinergic populations innervate the amygdala but it is unclear how these projections impact amygdala processes. Using optogenetic circuit-mapping strategies in ChAT-cre mice we demonstrate that amygdala-projecting basal forebrain and brainstem ChAT-containing neurons can differentially affect amygdala circuits and behavior. Photo-activating ChAT terminals in vitro revealed the underlying synaptic impact of brainstem inputs to the central lateral division to be excitatory, mediated via the synergistic glutamatergic activation of AMPA and NMDA receptors. In contrast, stimulating basal forebrain inputs to the basal nucleus resulted in endogenous ACh release resulting in biphasic inhibition-excitation responses onto principal neurons. Such response profiles are physiological hallmarks of neural oscillations and could thus form the basis of acetylcholine-mediated rhythmicity in amygdala networks. Consistent with this, in vivo NBm activation strengthened amygdala basal nucleus theta and gamma frequency rhythmicity, both of which continued for seconds after stimulation and were dependent on local muscarinic or nicotinic receptor activation, respectively. Activation of brainstem ChAT-containing neurons however resulted in a transient increase in central lateral amygdala activity that was independent of cholinergic receptors. In addition, driving these respective inputs in behaving animals induced opposing appetitive and defensive learning-related behavioral changes. Since learning and memory is supported by both cellular and network-level processes in central cholinergic and amygdala networks, these results provide a route by which distinct cholinergic inputs can convey salient information to the amygdala and promote associative biophysical changes that underlie emotional memories.


2017 ◽  
Vol 29 (1) ◽  
pp. 42-53 ◽  
Author(s):  
Nelson Espinosa ◽  
Alejandra Alonso ◽  
Cristian Morales ◽  
Pedro Espinosa ◽  
Andrés E Chávez ◽  
...  

2008 ◽  
Vol 100 (3) ◽  
pp. 1562-1575 ◽  
Author(s):  
M. Bazhenov ◽  
N. F. Rulkov ◽  
I. Timofeev

Cortical gamma oscillations in the 20- to 80-Hz range are associated with attentiveness and sensory perception and have strong connections to both cognitive processing and temporal binding of sensory stimuli. These gamma oscillations become synchronized within a few milliseconds over distances spanning a few millimeters in spite of synaptic delays. In this study using in vivo recordings and large-scale cortical network models, we reveal a critical role played by the network geometry in achieving precise long-range synchronization in the gamma frequency band. Our results indicate that the presence of many independent synaptic pathways in a two-dimensional network facilitate precise phase synchronization of fast gamma band oscillations with nearly zero phase delays between remote network sites. These findings predict a common mechanism of precise oscillatory synchronization in neuronal networks.


2019 ◽  
Author(s):  
Tamás Laszlovszky ◽  
Dániel Schlingloff ◽  
Panna Hegedüs ◽  
Tamás F. Freund ◽  
Attila Gulyás ◽  
...  

Basal forebrain cholinergic neurons (BFCN) densely innervate the forebrain and modulate synaptic plasticity, cortical processing, brain states and oscillations. However, little is known about the functional diversity of cholinergic neurons and whether distinct types support different functions. To examine this question we recorded BFCN in vivo, to examine their behavioral functions, and in vitro, to study their intrinsic properties. We identified two distinct types of BFCN that markedly differ in their firing modes, synchronization properties and behavioral correlates. Bursting cholinergic neurons (BFCNBURST) fired in zero-lag synchrony with each other, phase-locked to cortical theta activity and fired precisely timed bursts of action potentials after reward and punishment. Regular firing cholinergic neurons (BFCNREG) were found predominantly in the posterior basal forebrain, displayed strong theta rhythmicity (5-10 Hz), fired asynchronously with each other and responded with precise single spikes after behavioral outcomes. In an auditory detection task, synchronization of BFCNBURST neurons to auditory cortex predicted the timing of mouse responses, whereas tone-evoked cortical coupling of BFCNREG predicted correct detections. We propose that cortical activation relevant for behavior is controlled by the balance of two cholinergic cell types, where the precise proportion of the strongly activating BFCNBURST follows an anatomical gradient along the antero-posterior axis of the basal forebrain.


Author(s):  
Sylvie Polak-Charcon ◽  
Mehrdad Hekmati ◽  
Yehuda Ben Shaul

The epithelium of normal human colon mucosa “in vivo” exhibits a gradual pattern of differentiation as undifferentiated stem cells from the base of the crypt of “lieberkuhn” rapidly divide, differentiate and migrate toward the free surface. The major differentiated cell type of the intestine observed are: absorptive cells displaying brush border, goblet cells containing mucous granules, Paneth and endocrine cells containing dense secretory granules. These different cell types are also found in the intestine of the 13-14 week old embryo.We present here morphological evidence showing that HT29, an adenocarcinoma of the human colon cell line, can differentiate into various cell types by changing the growth and culture conditions and mimic morphological changes found during development of the intestine in the human embryo.HT29 cells grown in tissue-culture dishes in DMEM and 10% FCS form at late confluence a multilayer of morphologically undifferentiated cell culture covered with irregular microvilli, and devoid of tight junctions (Figs 1-3).


Sign in / Sign up

Export Citation Format

Share Document