Reticular stimulation and hippocampal theta rhythm in rats: Effects of drugs

doi:10.1016/0306-4522(78)90004-0

Neuroscience

Volume 3, Issue 7, July 1978, Pages 629-632

https://doi.org/10.1016/0306-4522(78)90004-0 Get rights and content

Abstract

The effect of drugs on hippocampal theta rhythm induced by high frequency stimulation of the midbrain reticular formation was investigated in free-moving rats. The linearity of the relationship between the frequency of theta produced and the intensity of the stimulating current was unchanged by injections of sodium amylobarbitone; however, the frequency itself was reduced. Cholinergic blockade or depletion of noradrenaline, dopamine or serotonin levels in brain did not produce such a reduction in frequency, nor did they change the linearity of the function.

These results contrast with the nonlinear effects which have been found with sodium amylobarbitone when septal stimulation is used to evoke theta rhythm; and with the fact that such nonlinear effects can be reproduced by depletion of forebrain noradrenaline levels. Sodium amylobarbitone appears, therefore, to affect control of hippocampal theta rhythm by actions on two systems, only one of which is dependent on noradrenaline. The duplication of behavioural effects of the drug by lesions of the dorsal ascending noradrenergic bundle may imply that the frequency at which theta occurs is less important for the control of such behaviours than other aspects of this electrical activity.

References (17)

JamesD.T.D. et al.
Septal driving of hippocampal theta rhythm as a function of frequency in the free-moving rat
Neuroscience
(1977)
KramisR. et al.
Two types of hippocampal rhythmical slow activity in both the rabbit and the rat: relations to behaviour and effects of atropine, diethyl ether, urethane and pentobarbital
Expl Neurol.
(1975)
McNaughtonN. et al.
Septal driving of hippocampal theta rhythm as a function of frequency in the male rat: effects of drugs
Neuroscience
(1977)
BrückeF. et al.
Die Beeinflussung der ‘Hippocampus-arousal-Reaktion’ beim Kaninchen durch elektrische Reizung im Septum
Pflügers Arch. ges. Physiol.
(1959)
GrayJ.A.
Sodium amobarbital, the hippocampal theta rhythm and the partial reinforcement extinction effect
Psychol. Rev.
(1970)
GrayJ.A.
The structure of the emotions and the limbic system
GrayJ.A.
Drug effects on fear and frustration: possible sites of action of minor tranquillisers
GrayJ.A. et al.
Frequency specific relation between hippocampal theta rhythm, behaviour and amobarbital action
Science, N.Y.
(1970)

There are more references available in the full text version of this article.

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It was demonstrated, that that a correlation exists between the intensity of hypothalamic stimulation and HPC theta frequency. An increase in the frequency of hippocampal theta oscillations was observed when higher current or voltage was used to stimulate the posterior hypothalamic region (Bland and Vanderwolf, 1972; Whishaw et al., 1972; McNaughton and Sedgwick, 1978; Destrade and Ott, 1981; Vertes, 1981; Smythe et al., 1991; Bland et al., 1994; Oddie et al., 1994). This voltage of stimulation to resultant hippocampal theta frequency relation suggested that PHa may be involved in theta frequency coding.
Theta rhythm recorded as an extracellular synchronous field potential is generated in a number of brain sites including the hippocampus. The physiological occurrence of hippocampal theta rhythm is associated with the activation of a number of structures forming the ascending brainstem-hippocampal synchronizing pathway. Experimental evidence indicates that the supramammillary nucleus and posterior hypothalamic nuclei, considered as the posterior hypothalamic area, comprise a critical node of this ascending pathway. The posterior hypothalamic area plays an important role in movement control, place-learning, memory processing, emotion and arousal. In the light of multiplicity of functions of the posterior hypothalamic area and the influence of theta field oscillations on a number of neural processes, it is the authors’ intent to summarize the data concerning the involvement of the supramammillary nucleus and posterior hypothalamic nuclei in the modulation of limbic theta rhythmicity as well as the ability of these brain structures to independently generate theta rhythmicity.
Laterality of an EEG anxiety disorder biomarker largely follows handedness
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Absent biological criteria, treatment response rates are poor (Bystrirsky, 2013) and new approaches with biomarkers based on neuropsychology and fundamental neural-level dysfunction are needed (Insel, 2013; Insel et al., 2010). Using as a foundation the effects of drugs that are anxiolytic in the clinic, we have developed over several decades (Gray, 1977, 1982; Gray & McNaughton, 2000; Gray, McNaughton, James, & Kelly, 1975; McNaughton & Corr, 2004; McNaughton, DeYoung, & Corr, 2016; McNaughton & Sedgwick, 1978; Silva & McNaughton, 2019) a detailed neuropsychology of a Behavioural Inhibition System (BIS) that controls a form of anxiety. This neuropsychology emphasises goal conflict (e.g. approach-avoidance, see McNaughton et al., 2016, section 1.1 for a detailed discussion of goals); sees goal conflict resolution as a distinct defensive process (Gray & McNaughton, 2000 – fig. 1.1, p4; fig. 5.1, p86); accounts for variations in both adaptive and dysfunctional defensive reactions in both rodents and humans; predicts a range of distinct biological types of threat-related disorder; and is consistent both with a large body of rodent data and with recent human imaging of threat processing and trait anxiety (Fung, Qi, Hassabis, Daw, & Mobbs, 2019; Korn & Bach, 2019; McNaughton, 2019).
Anxiety disorders are the most common mental disorders impacting people worldwide. Using an auditory Stop Signal Task (SST), we have developed an anxiety disorder biomarker (goal-conflict specific rhythmicity/GCSR) that occurs at the right frontal site F8 in right-handed participants. Here, we compare its laterality in left-handers (n = 26) versus demographically-matched right-handers (n = 26) between the ages of 18–30. We assessed the effects on GCSR power of the handedness of the participants (left or right), blocks of the SST, left–right variation across frontal channels (F7, F3, Fz, F4, F8), and EEG frequency (4–12 Hz). Left-handers differed from right-handers most at the channels furthest from the midline. This difference was largely a mirroring of right hander responses by left handers. With frontal channels coded in reverse order for left handers the original significant differences disappeared. Some differences remained between the groups in the frequency variation across blocks of testing. These and other data suggest that the circuitry engaged by conflict in the SST is different from that directly controlling stopping behaviour. Our results also suggest that where GCSR is used as an anxiety process or disorder biomarker in groups that combine both left and right-handed people, data only from the channel ipsilateral to the dominant hand should be used (F7, or F8, respectively).
Mixed Effects of Low-dose Ethanol on Cortical and Hippocampal Theta Oscillations
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Ethanol reduces the slope of the linear relationship between RPO stimulation intensity and HPC theta frequency likely via an action on a benzodiazepine site (Coop et al., 1990). The RPO-elicitation paradigm is highly robust and specific in terms of predicting human clinical anxiolytic action (McNaughton and Sedgwick, 1978; Gray and McNaughton, 2000; McNaughton et al., 2007), and has been used in a range of laboratories as a screen of known or potential anxiolytic drugs (Engin et al., 2009; Siok et al., 2009, 2012; Yeung et al., 2012). More recently, anxiolytics have also been shown to reduce HPC theta frequency related to the speed of locomotion (Wells et al., 2013) – a well-established and robust behavioural correlate of HPC theta oscillations (Vanderwolf, 1969; McFarland et al., 1975; Slawinska and Kasicki, 1998; Robbe et al., 2006; Hinman et al., 2011; Wells et al., 2013).
Ethanol is one of the most widely used drugs – with many psychoactive effects, including anxiolysis. The deleterious effects on brain function and general health of chronic and high-level ethanol use are well-studied. However, the neurophysiology of acute low dose ethanol has not been systematically investigated. Here, we examined the effects of low dose (0.25 and 0.5 g/kg) ethanol on midline (prefrontal, cingulate and retrosplenial) neocortical and hippocampal theta oscillations in freely moving rats. We also tested low dose ethanol on reticular-elicited and running-elicited hippocampal theta frequency and assessed the linear relationship of theta frequency to stimulation intensity and running speed, respectively. Low dose ethanol had mixed effects on neocortical theta oscillations. It most reliably reduced theta frequency, produced a weak inverted-U effect on theta power, and had no detectable effect on cortico-hippocampal theta coherence. Ethanol dose-dependently decreased the y-intercept of the speed-theta frequency function without affecting the slope, but decreased the slope of the stimulation intensity-theta frequency function without affecting the y-intercept; thus decreasing theta frequency in both cases. We conclude low dose ethanol has weak but detectable effects on neocortical and hippocampal theta oscillations. These effects may underlie positive cognitive and behavioural outcomes reported in the literature using low dose ethanol. The double dissociation of slope and y-intercept specific changes relating to different methods of hippocampal theta elicitation presents the potential to probe multiple mechanisms contributing to anxiolytic effects on theta and so hippocampal function.
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Consolidation studies show that, over time, memory recall becomes independent of the medial temporal lobes. Multiple lines of research show that the medial frontal cortex, including the anterior cingulate cortex (ACC), is involved with contextual information processing and remote recall. We hypothesize that interactions between the ACC and hippocampal area CA1 will change as memories became more remote. Animals are re-exposed to multiple environments at different retention intervals. During remote recall, ACC-CA1 theta coherence increases, with the ACC leading area CA1. ACC theta regulates unit spike timing, gamma oscillations, and ensemble and single-neuron information coding in CA1. Over the course of consolidation, the strength and prevalence of ACC theta modulation grow, leading to richer environmental context representations in CA1. These data are consistent with the transference of contextual memory dependence to the ACC and indicate that remote memories are retrieved via ACC-driven oscillatory coupling with CA1.
Ventral hippocampal histamine increases the frequency of evoked theta rhythm but produces anxiolytic-like effects in the elevated plus maze
2016, Neuropharmacology
The neurobiological underpinnings of anxiety are of paramount importance to the development of effective therapeutic treatments. To date, there is considerable pharmacological evidence suggesting that the suppression of hippocampal theta frequency is a robust and predictive assay of anxiolytic drug action. Recently, this idea has been challenged using histamine (2-(4-imidazolyl)ethanamine), an endogenous neurotransmitter involved in a number of brain and behavioral functions. Here, we systematically evaluate the effects of dorsal and ventral hippocampal histamine infusions on evoked theta frequency and behavioral anxiety. Given the complex pharmacological profile of histamine and its receptors in the hippocampus, we reasoned that local intra-hippocampal infusions would be a powerful test of the theta suppression model. While dorsal hippocampal infusions of histamine produced neither significant changes in anxious-like behavior in the elevated plus maze nor changes of evoked theta, ventral infusions of histamine produced potent behavioral anxiolysis which corresponded to an increase, and not a decrease, in evoked theta frequency. As a positive neurophysiological control, we demonstrated that diazepam, a proven anxiolytic drug, decreased the frequency of hippocampal theta following both dorsal and ventral hippocampal infusions. Our results further challenge the hippocampal theta frequency suppression model as a measure of anxiolytic drug action.
This article is part of the Special Issue entitled ‘Histamine Receptors’.
GABA-A receptor modulators alter emotionality and hippocampal theta rhythm in an animal model of long-lasting anxiety
2013, Brain Research
The cholinergic system is implicated in emotional regulation. The injection of non-convulsant doses of the muscarinic receptor agonist pilocarpine (PILO) induces long-lasting anxiogenic responses in rats evaluated at different time-points (24 h to 3 months). To investigate the underlying mechanisms, rats treated with PILO (150 mg/kg) were injected 24 h or 1 month later with an anxiolytic (diazepam, 1 mg/kg, DZP) or anxiogenic (pentylenetetrazole, 15 mg/kg, PTZ) drug and evaluated in the elevated plus-maze (EPM). Prefrontal cortex (PFC) and hippocampal (HIP) electroencephalographic recordings and acetylcolinesterase (AChE) activity were also analyzed after PILO treatment. Anxiogenic responses observed in the EPM 24 h or 1 month after PILO treatment (e.g., decreased time spent and number of entries into the open arms of the maze) were blocked by DZP but not affected by PTZ. No epileptiform events were registered in the HIP or PFC at 24 h or 1 month after PILO injection, but enhanced theta activity was observed in the HIP. DZP decreased hippocampal theta of PILO-treated rats in contrast with PTZ, which increased this parameter in saline- and PILO-treated rats. The HIP and PFC AChE activity did not change after PILO treatment. Our findings demonstrate that the long-term effects on the emotionality of rats induced by PILO are associated with electrophysiological changes in the HIP and sensitive to pharmacological manipulation of the GABAergic system. The present work may support this new research model of long-lasting anxiety, while also highlighting the muscarinic system as a potential target involved in anxiety disorders.

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Reticular stimulation and hippocampal theta rhythm in rats: Effects of drugs

Abstract

Neuroscience

Expl Neurol.

Neuroscience

Die Beeinflussung der ‘Hippocampus-arousal-Reaktion’ beim Kaninchen durch elektrische Reizung im Septum

Pflügers Arch. ges. Physiol.

Sodium amobarbital, the hippocampal theta rhythm and the partial reinforcement extinction effect

Psychol. Rev.

The structure of the emotions and the limbic system

Drug effects on fear and frustration: possible sites of action of minor tranquillisers

Frequency specific relation between hippocampal theta rhythm, behaviour and amobarbital action

Science, N.Y.