House of Mind

"Biology gives you a brain. Life turns it into a mind" - Jeffrey Eugenides

  • 11th July
    2011
  • 11
The Science of Sleep: A Focus on REM Sleep and Dreaming (Click on the image for a better view) As anybody who was gone without sleep for a couple of days would know, sleep is essential for mental health and adequate cognitive function. Regulation of the sleep cycle (and consciousness states) is influenced by monoamines (i.e. serotonin, noradrenaline, histamine, dopamine) and their interaction with cholinergic neurons in the brainstem. There are 3 types of transitions in consciousness identifiable in the human brain: waking, rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. Sleep, particularly REM sleep, has been suggested to be important for brain development by contributing to plasticity processes in the brain and is thought to have a role in memory processing (particularly state dependent memory consolidation).  REM sleep is sleep that results in brain activation, as indexed by electroencephalographic evidence, but with inhibition of muscle tone and (involuntary) saccadic eye movements. REM sleep is regulated by two distinct neuronal populations: REM-off cells: Active during waking and inactive during REM sleep. Located in the locus coeruleus and the dorsal raphe nucleus and usually serotonergic/noradrenergic neurons. REM-on cells: Inactive during waking and active during REM sleep. Located primarily in the mesopontine tegmentum and usually cholinergic neurons.  As indicated above, REM sleep is controlled by the brainstem pontine nuclei and is potentiated by cholinergic mechanisms (REM-on)  while being suppressed by aminergic mechanisms (REM-off). Thus, transitions in states of consciousness (i.e. wakefulness, NREM, REM) are the result of these neuromodulatory neurotransmitter interactions in the “sleep centers” of the brain. REM sleep is also characterized by the minimal levels of inhibition present in the brain during this stage.REM sleep activates phasic signals (PGO waves) in the pontine brainstem (P), the lateral geniculate body of the thalamus (G), and the occipital cortex (O), which are also prominent in the visual system and in sensorimotor systems in the forebrain. PGO waves are thought to help maintenance of sleep by occluding external sensory input in addition to fostering sensorimotor integration that may be important for perception and motor control.  Evidence from neuroimaging studies have found increased activation (as indexed by blood flow increases) in several brain areas during REM sleep. These include: the pons, the midbrain, the thalamus and hypothalamus, the amygdala and the basal ganglia. It is important to also keep in mind that REM sleep (along with dreaming occuring during REM) induces activation in the forebrain through ascending arousal systems and that this activation is aminergically deficient and cholinergically driven, as depicted in the image above. For a long period of time, REM sleep was thought of as the “sleep substrate” of dreaming, which may have been due to the higher reports of dreaming sequences during REM sleep compared to NREM sleep. A popular model that dominated the field was Hobson’s Activation-Hypothesis Model, which stated that dreams are actively generated by the brainstem and passively synthesized by the forebrain. However, there is growing evidence supporting the notion that REM sleep and dreaming are dissociable states controlled by different neural mechanisms: REM sleep by cholinergic mechanisms in the brain stem and dreaming sequences via dopaminergic mechanisms in the forebrain. In his 2000 review, Solms lists several of the arguments in favor of this REM sleep-dream association. Some of these are: REM sleep is not controlled by forebrain mechanisms: Classical studies (Jouvet, 1962) have shown that the forebrain is both incapable of and unnecessary for generating REM sleep.  Not all dreaming is correlated with REM sleep: REM can occur in the absence of dreaming and dreaming can occur in the absence of REM sleep (NREM).  Dreaming is preserved in subjects with large pontine brain stem lesions: Manifestations of REM sleep, however, are eliminated. Dreaming is only eliminated when components of both REM and NREM sleep are ablated.  Dreaming is eliminated by forebrain lesions that completely spare the brainstem: These lesions were typically in the parieto-temporo-occipital (PTO) junction, a region that supports several cognitive processes vital for the construction of mental imagery. However, the REM sleep cycle is preserved.  Dreams are actively generated by forebrain mechanisms unrelated to REM sleep. The dopaminergic innervation in these forebrain networks originates from the VTA, the source of mesocortical/mesolimbic dopamine. Descending components of these loops come from latter brain areas that are heavily influenced by cholinergic circuit activity. Chemical activation of this dopamine circuit through L-dopa has been shown to promote psychotic symptoms and increase dreaming, which suggests a causal relationship between mesolimbic/mesocortical DA and dreaming. Dreams are generated by a specific network of forebrain structures: It has been postulated that dreaming involves concerted activity in highly specific group of forebrain structures which include: anterior and lateral hypothalamic areas, the amygdaloid complex, septal-ventral striatal areas, as well as infralimbic, prelimbic, orbitofrontal, anterior cingulate, entorhinal, insular and occipitotemporal cortical areas. Considering all the implicated areas, the construction of imagery during dreaming is a complex cognitive process.  To sum up, dreaming seems to require: 1) brain activation (not necessarily REM sleep) along with the 2) engagement of specific dopamine circuits in the forebrain that initiate dreaming. Sources:  Hobson, J.A. 2009. REM sleep and dreaming: Towards a theory of protoconsciousness. Nature Reviews Neuroscience. 10: 803-813. doi:10.1038/nrn271 Hobson, J.A. & Pace-Schott, EF. 2002. The cognitive neuroscience of sleep: neuronal systems, consciousness and learning. Nature Reviews Neuroscience. 3 (9): 679-693. doi:10.1038/nrn915 Solms, Mark. 2000. Dreaming and REM sleep are controlled by 2 different brain mechanisms. Behavioral and Brain Sciences. 23: 843-850. 

The Science of Sleep: A Focus on REM Sleep and Dreaming

(Click on the image for a better view)

As anybody who was gone without sleep for a couple of days would know, sleep is essential for mental health and adequate cognitive function. Regulation of the sleep cycle (and consciousness states) is influenced by monoamines (i.e. serotonin, noradrenaline, histamine, dopamine) and their interaction with cholinergic neurons in the brainstem. There are 3 types of transitions in consciousness identifiable in the human brain: waking, rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. Sleep, particularly REM sleep, has been suggested to be important for brain development by contributing to plasticity processes in the brain and is thought to have a role in memory processing (particularly state dependent memory consolidation). 

REM sleep is sleep that results in brain activation, as indexed by electroencephalographic evidence, but with inhibition of muscle tone and (involuntary) saccadic eye movements. REM sleep is regulated by two distinct neuronal populations:

  • REM-off cells: Active during waking and inactive during REM sleep. Located in the locus coeruleus and the dorsal raphe nucleus and usually serotonergic/noradrenergic neurons.
  • REM-on cells: Inactive during waking and active during REM sleep. Located primarily in the mesopontine tegmentum and usually cholinergic neurons. 

As indicated above, REM sleep is controlled by the brainstem pontine nuclei and is potentiated by cholinergic mechanisms (REM-on)  while being suppressed by aminergic mechanisms (REM-off). Thus, transitions in states of consciousness (i.e. wakefulness, NREM, REM) are the result of these neuromodulatory neurotransmitter interactions in the “sleep centers” of the brain.

REM sleep is also characterized by the minimal levels of inhibition present in the brain during this stage.REM sleep activates phasic signals (PGO waves) in the pontine brainstem (P), the lateral geniculate body of the thalamus (G), and the occipital cortex (O), which are also prominent in the visual system and in sensorimotor systems in the forebrain. PGO waves are thought to help maintenance of sleep by occluding external sensory input in addition to fostering sensorimotor integration that may be important for perception and motor control. 

Evidence from neuroimaging studies have found increased activation (as indexed by blood flow increases) in several brain areas during REM sleep. These include: the pons, the midbrain, the thalamus and hypothalamus, the amygdala and the basal ganglia. It is important to also keep in mind that REM sleep (along with dreaming occuring during REM) induces activation in the forebrain through ascending arousal systems and that this activation is aminergically deficient and cholinergically driven, as depicted in the image above.

For a long period of time, REM sleep was thought of as the “sleep substrate” of dreaming, which may have been due to the higher reports of dreaming sequences during REM sleep compared to NREM sleep. A popular model that dominated the field was Hobson’s Activation-Hypothesis Model, which stated that dreams are actively generated by the brainstem and passively synthesized by the forebrain. However, there is growing evidence supporting the notion that REM sleep and dreaming are dissociable states controlled by different neural mechanisms: REM sleep by cholinergic mechanisms in the brain stem and dreaming sequences via dopaminergic mechanisms in the forebrain. In his 2000 review, Solms lists several of the arguments in favor of this REM sleep-dream association. Some of these are:

  1. REM sleep is not controlled by forebrain mechanisms: Classical studies (Jouvet, 1962) have shown that the forebrain is both incapable of and unnecessary for generating REM sleep. 
  2. Not all dreaming is correlated with REM sleep: REM can occur in the absence of dreaming and dreaming can occur in the absence of REM sleep (NREM). 
  3. Dreaming is preserved in subjects with large pontine brain stem lesions: Manifestations of REM sleep, however, are eliminated. Dreaming is only eliminated when components of both REM and NREM sleep are ablated. 
  4. Dreaming is eliminated by forebrain lesions that completely spare the brainstem: These lesions were typically in the parieto-temporo-occipital (PTO) junction, a region that supports several cognitive processes vital for the construction of mental imagery. However, the REM sleep cycle is preserved. 
  5. Dreams are actively generated by forebrain mechanisms unrelated to REM sleep. The dopaminergic innervation in these forebrain networks originates from the VTA, the source of mesocortical/mesolimbic dopamine. Descending components of these loops come from latter brain areas that are heavily influenced by cholinergic circuit activity. Chemical activation of this dopamine circuit through L-dopa has been shown to promote psychotic symptoms and increase dreaming, which suggests a causal relationship between mesolimbic/mesocortical DA and dreaming.
  6. Dreams are generated by a specific network of forebrain structures: It has been postulated that dreaming involves concerted activity in highly specific group of forebrain structures which include: anterior and lateral hypothalamic areas, the amygdaloid complex, septal-ventral striatal areas, as well as infralimbic, prelimbic, orbitofrontal, anterior cingulate, entorhinal, insular and occipitotemporal cortical areas. Considering all the implicated areas, the construction of imagery during dreaming is a complex cognitive process. 

To sum up, dreaming seems to require: 1) brain activation (not necessarily REM sleep) along with the 2) engagement of specific dopamine circuits in the forebrain that initiate dreaming.

Sources: 

Hobson, J.A. 2009. REM sleep and dreaming: Towards a theory of protoconsciousness. Nature Reviews Neuroscience. 10: 803-813. doi:10.1038/nrn271

Hobson, J.A. & Pace-Schott, EF. 2002. The cognitive neuroscience of sleep: neuronal systems, consciousness and learning. Nature Reviews Neuroscience. 3 (9): 679-693. doi:10.1038/nrn915

Solms, Mark. 2000. Dreaming and REM sleep are controlled by 2 different brain mechanisms. Behavioral and Brain Sciences. 23: 843-850. 

  • 16th November
    2010
  • 16

The Effects of Corticotropin-Releasing Factor on Dopamine Release: Implications for Reward and Effort

Take home messages: 

  • Corticotropin releasing factor (CRF) acts in the ventral tegmental area (VTA), a primary source of dopaminergic neurons and an integral part of the mesolimbic reward pathway, to regulate dopamine (DA) neurotransmission. 
  • A large reward (large reward magnitude)  will enhance motivated behavior. 
  • A large reward magnitude also enhances DA release in response to cues and rewards.
  • CRF, a hormone and neurotransmitter implicated in the stress response (HPA axis), in the VTA will attenuate motivated behavior in a dose-dependent manner and this effect is not due to motor suppression. 
  • CRF in the VTA attenuates phasic DA release (burst DA release as opposed to a more gradual release) specifically to rewards, not the cues related to the rewards. 
  • Satiety (being full) will reduce motivated behavior (in this case the reward was food pellets) as well as DA release to rewards (but not cues). 

Author Abstract (Phillips, et. al) : Phasic dopamine release during reward and effort manipulations: Effects of corticotropin release factor. 

The effort an individual is willing to exert to obtain a reward is dependent upon one’s motivational state as well as the value of the reward. Contemporary theories of dopamine function suggest that dopamine release, particularly in the striatum, is involved with enabling high-effort behaviors. Motivated behaviors can be influenced by stressful stimuli and stress-released neuropeptides such as corticotropin-releasing factor (CRF). The behavioral effects of stress on motivation could involve the midbrain dopamine system as (i) stress increases dopamine levels, (ii) CRF is released into the midbrain during stress, and (iii) CRF increases the firing rate and potentiates glutamate receptor current in dopamine neurons. Thus, we hypothesized that CRF in the VTA will elevate phasic dopamine release and increase the effort exerted to obtain a reward. However, before addressing this pharmacological question it was important to first determine how natural manipulations of motivational state and reward magnitude influence phasic dopamine release during high-effort behaviors.

We utilized fast-scan cyclic voltammetry to examine phasic striatal dopamine release to rewards and reward-predictive cues in rats performing an operant task under a progressive ratio (PR) reinforcement schedule for natural reinforcers. In separate sessions, we assessed behavior and dopamine release in rats under different motivational states (food-deprived or free-fed) or working for rewards of different magnitudes. The cumulative number of rewards earned scaled with the reward size in a given PR session. Interestingly, we found that motivational state and reward size robustly scaled reward-evoked dopamine release, while cue-evoked dopamine release was less sensitive to these manipulations. After establishing the effect of natural manipulations, we next examined how CRF injections into the midbrain affected behavior and dopamine release during PR sessions. Contrary to our hypothesis, CRF injected into the midbrain lowered the breakpoint in PR sessions. Furthermore, CRF injections attenuated reward-evoked dopamine release but did not affect cue-evoked dopamine release. Together, these results suggest that CRF modulates motivated behavior by affecting either dopamine neurons responsive to reward delivery and/or inputs to the midbrain representing the delivery of rewards.