Download Histamine reduces firing and bursting of anterior and intralaminar

Behavioural Brain Research 124 (2001) 137– 143
www.elsevier.com/locate/bbr
Histamine reduces firing and bursting of anterior and intralaminar
thalamic neurons and activates striatal cells in anesthetized rats
Nora Sittig, Helga Davidowa *
Johannes-Mueller-Institute of Physiology, Charité, Faculty of Medicine, Humboldt Uni6ersity Berlin, Tucholskystr. 2, D-10117 Berlin, Germany
Received 3 June 2000; accepted 4 July 2000
Abstract
Histamine is known to play a role in the regulation of waking behavior as well as in processes of memory and reinforcement.
The striatum and thalamic nuclei as the intralaminar complex and the anterior group can be involved in these functions. Little
is known about the action of histamine on neurons of these brain structures. Single unit activity was extracellularly recorded in
rats anesthetized with urethane. Firing of anterior and intralaminar thalamic neurons that responded to iontophoretically
administered histamine was predominantly reduced (Wilcoxon test (Wt), P B 0.05, n = 49 and 63, respectively), whereas striatal
neurons were mainly activated by the drug (Wt, PB 0.05, n=29). Thalamic neurons also significantly reduced the number of
burst discharges and the proportion of spikes involved in bursts. The histaminergic effects could be blocked by H1 or H2 receptor
antagonists. In conclusion, histamine may control waking behavior also via nonspecific thalamic nuclei and basal ganglia circuits.
Through modulation of the transmission in the anterior thalamus it may exert an influence on learning and emotional processes.
© 2001 Elsevier Science B.V. All rights reserved.
Keywords: Single unit activity; Burst discharges; Caudate-putamen; Iontophoresis; Histamine receptor antagonists
1. Introduction
The histaminergic system of the brain originating
from the tuberomammillar hypothalamic nucleus [47] is
known to be involved in the regulation of sleep and
wakefulness, processes of learning and memory, locomotion and reward [3,12,24,42,45,50]. The knowledge
of sedative effects of antihistaminergic substances therapeutically used has on the one hand induced attempts
to evolve drugs not crossing the blood – brain barrier,
on the other hand it has activated the study of brain
functions of histamine. Also the action of antihistamines as psychotropic drugs points to the involvement of histamine in a variety of functions.
Neurons of the tuberomammillary nucleus are spontaneously active [43]. In freely moving rats they release
histamine especially in the dark period, starting a gradual increase in the second half of the light period [22].
* Corresponding author. Tel.: + 49-30-28026620; fax: +49-3028026669.
E-mail address: [email protected] (H. Davidowa).
This circadian rhythm suggests an involvement of histamine in normal regulation of sleep and waking periods. Furthermore, the hypothalamic suprachiasmatic
nucleus known as circadian pacemaker is densely innervated by histaminergic fibers, and its neurons are predominantly activated by histamine acting on H1
receptors [37]. On the other hand, tuberomammillar
neurons are innervated from the brainstem and several
structures of the limbic system [30]. Thus, the release of
histamine may be modulated in connection with limbic
functions.
There are a lot of data speaking in favor of the
importance of histamine for arousal [17,18,24,34]. Concerning learning and memory there are differing reports. It has been shown that histamine facilitates long
term potentiation in the hippocampus [1,44] and improves learning and memory [33,42]. On the other
hand, there are results that underline an inhibitory
function of histamine in the control of reinforcement
and mnemonic processes [12,50].
Due to their connections, thalamic neurons can be
involved in processes of arousal as well as of memory
0166-4328/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 1 6 6 - 4 3 2 8 ( 0 1 ) 0 0 2 2 3 - 6
138
N. Sittig, H. Da6idowa / Beha6ioural Brain Research 124 (2001) 137–143
and reward. The group of anterior nuclei consisting of
the anteromedial, anterodorsal and anteroventral nucleus represents the hypothalamic relay to the cortex
[40]. The laterodorsal nucleus is associated to these
nuclei because of connectional and functional similarities. These nuclei project to cingulate areas of the
cerebral cortex and get a feedback through the
hippocampal formation [40]. These circuits are found to
play a role in learning and emotion [46]. The intralaminar thalamic system is involved in the regulation of
waking behavior and accompanying changes in cortical
synchronization/desynchronization [9,38]. There are
very few studies on the effects of histamine on thalamic
neurons [10] except on the lateral geniculate nucleus
[21].
There is evidence of a histaminergic innervation of
thalamic nuclei [29,47], but the existence of the H1 and
H2 receptor subtypes of histamine could not be clearly
shown in all nuclei of the rat thalamus [28,45] in
contrast to the occurrence of H3 receptors [32]. Therefore, we wanted to know how far H1 and H2 receptor
antagonists can block histaminergic effects in the
thalamus.
Since the firing mode of thalamic neurons may vary
between regular firing during wakefulness and the formation of bursts during sleep [21,38,39], we analyzed
the discharge pattern. The occurrence of groups of
action potentials (bursts) after a long period of hyperpolarization can depend on activation of low-threshold
calcium channels [13,20]. In depolarized neurons, normal high-threshold bursts of action potentials may
develop.
Furthermore, since intralaminar neurons do not only
innervate cortical areas, but also the basal ganglia
[6,16], especially the caudate-putamen being important
for motor and cognitive functions [2], we were interested in knowing direct in-vivo effects of histamine on
the striatum.
2. Materials and methods
Adult male Wistar rats (250–400 g) were anesthetized with urethane (1.2 g/kg i.p., supplemental
doses as required). Rectal temperature was maintained
at 37–38°C. The experiments were carried out as described earlier [4,5] in accordance with international
standards of animal welfare and approved by the regional Berlin animal ethics committee (G 0251/95).
The head of the rat was fixed in a stereotaxic device.
Four holes were drilled into the bone overlying the
thalamus and the striatum. Single unit activity was
extracellularly recorded by means of a glass microelectrode filled with a solution of trypan blue that was used
to mark the recording positions. The action potentials
were amplified, monitored and discriminated using con-
ventional methods. A multibarrel electrode affixed to
the recording electrode was used for the iontophoretic
ejection of the following drugs: histamine dihydrochloride, the H1 receptor antagonist mepyramine maleate
and the H2 receptor antagonist cimetidine, in several
cases also dimaprit dihydrochloride, H2 receptor agonist, and (R)-(− )-a-methylhistamine dihydrobromide,
H3 receptor agonist. All drugs (0.1 M, pH 4.5) were
ejected with positive currents from 5 to 90 nA. One
barrel was filled with sodium chloride (165 mM) for
balance and current control. Retaining currents (5 nA)
of opposite polarity were applied between the ejection
periods.
At the end of the experiment, the animals were given
a lethal dose of urethane and decapitated. The brains
were fixed with a solution of 10% paraformaldehyde.
The marked recording positions were histologically determined in frontal frozen sections by means of the
stereotaxic atlas [31].
The discharge rate of a neuron was determined for
periods of 100 s duration before (control), and during
ejection (early response), and in two periods after termination of the administration of drugs (late response and
recovery). Neurons that changed their discharge rate by
more than 25% (or at least by 0.5 impulses per s when
firing at a rate below 1 spike per s) during at least one
response period were regarded as being responsive to
the applied drug. The prevailing direction of changes in
all neurons of one population was proved with the
Wilcoxon paired rank sum test (Wt). All neurons irrespective of their responsiveness were included in this
test. Differences were considered to be statistically significant at PB 0.05 (two-tailed).
In some of the neurons that were responsive to
histamine we tried to prevent this effect by coadministration of histamine with one of the histamine receptor
antagonists. A reduction of the effect of histamine by
more than 25% (or by more than 70% for neurons with
a discharge rate below 1 impulse per s) was judged as
antagonization. The medians as well as the mean9
standard deviation (S.D.) of the discharge rates during
the different conditions were calculated from the data
of neuronal populations.
Furthermore, the discharge pattern of thalamic neurons was analyzed [4] by determining the number of
bursts in each 100 s period (Spike 2 software, burst
analysis program (Cambridge Electronic Design, UK)).
A sequence of spikes with an interspike interval 54 ms
was regarded as burst as recommended in the literature
[20]. Also the number of spikes within a burst and the
percentage of spikes involved in bursts was determined.
Additionally, the silent period prior to a burst was
measured. Bursts occurring after a silent period \100
ms possibly starting with a low-threshold Ca++ spike
were named LTS, in contrast to bursts with possibly
high-threshold spikes (HTS).
N. Sittig, H. Da6idowa / Beha6ioural Brain Research 124 (2001) 137–143
139
rons were mainly activated by histamine (Wt, PB0.01,
n=29). It caused in 14 cells (46.7%) a change in the
firing frequency by more than 25%, 12 increased; two
decreased (means and medians in Table 1). Also very
slowly discharging striatal neurons (less than 1 spike
per s) responded to histamine.
3.2. Effects of histamine receptor antagonists and
agonists
Fig. 1. Discharge rate (spikes per 3 s) of a centrolateral neuron.
Abscissa: time (bar at the bottom: 5 min). Bars: duration of administration of the drugs; numbers: current in nA. The neuron was
inhibited by histamine (Hist). This effect was not blocked by the H1
receptor antagonist Mepyramine (Mep), but with the H2 receptor
antagonist cimetidine (Cim) applied with a higher current.
3. Results
3.1. Effects of histamine on firing rate
Discharge rates of 141 histologically verified neurons
were recorded. They were located in the anterior thalamus (anterodorsal, -ventral, -medial and laterodorsal,
n= 49) and intralaminar thalamic nuclear complex
(centromedial, centrolateral, paracentral and parafascicular nuclei, n=63) as well as in the striatum (n =29).
The neuronal firing rate was predominantly reduced by
histamine in thalamic neurons (anterior: Wt, P B0.01,
n = 49; intralaminar: Wt, P B0.02, n =63). A change in
the discharge rate by more than 25% was observed in
27 anterior cells (55.1%), 17 decreased and eight increased firing, two cells showed a biphasic response.
Similarly, about two thirds of responsive intralaminar
neurons reduced firing (n = 23) (Fig. 1), one third increased it (n=12), one cell responded in a biphasic
manner. Means and medians of firing of the neuronal
populations are given in Table 1. It is to mention that
the values do not provide the maximal response, since
they were determined for given periods. Striatal neu-
Histamine receptor antagonists were applied to 27
thalamic neurons that were responsive to histamine. In
19 neurons (70%) the effects of histamine could be
reduced or prevented by coadministration with mepyramine or cimetidine. The H1 receptor antagonist
mepyramine reduced the inhibitory effect of histamine
in eight of 16 neurons tested, cimetidine was effective in
six of 11 neurons. In one neuron, both antagonists
could prevent the action of histamine. Fig. 1 shows an
inhibition of a centrolateral thalamic neuron by histamine and the antagonizing effect of cimetidine. The
activating effect of histamine could be reduced or prevented by mepyramine in six of seven cells, cimetedine
was not effective in one cell tested. Fig. 2 shows the
means of neuronal firing rates demonstrating the antagonizing effect. Blocking effects of the H1 as well as the
H2 receptor antagonist could be seen in both anterior
as well as intralaminar neurons.
The involvement of H2 receptors in the mediation of
histaminergic effects could also be shown by use of the
H2 receptor agonist dimaprit that activated three and
inhibited two of 15 cells in the anterior thalamus. In the
intralaminar complex, five of 25 cells were activated
and one cell inhibited. Out of the neurons activated by
dimaprit, four were inhibited by histamine. Effects of
dimaprit were especially observed in the centromedial
nucleus. In few cells tested, the H3 receptor agonist was
also effective, the drug activated two and inhibited two
of seven neurons.
In the striatum, the H1 receptor antagonist blocked
the activation induced by histamine in three out of five
neurons tested. In two neurons, cimetidine also had an
antagonistic effect. The suppressive effect of histamine
on one neuron could be blocked by the H1 receptor
antagonist. Only one of 12 neurons tested was activated
by the H2 receptor agonist.
Table 1
Discharge rates observed in neuronal populations of the anterior and intralaminar thalamus and the striatum
Spontaneous
Histamine
Late response
Recovery
Anterior neurons (n= 49)
Intralaminar neurons (n = 63)
Striatal neurons (n = 29)
Mean9S.D.
Median
Mean 9S.D.
Median
Mean9 S.D.
Median
3.85 94.16
3.559 4.09
3.329 3.79
3.859 3.9
3.03
2.24
2.04
3.12
1.63 9 1.2
1.40 91.2
1.43 9 1.4
1.64 9 1.3
1.44
0.98
1.05
1.22
3.20 93.8
3.64 9 4.1
3.77 9 4.0
3.30 93.6
1.8
2.3
2.3
2.6
140
N. Sittig, H. Da6idowa / Beha6ioural Brain Research 124 (2001) 137–143
Fig. 3. Bursts (sequences of potentials with an interspike interval B 4
ms) and spikes of two intralaminar thalamic neurons during different
conditions. Abscissa: time (bar: 100 s). The periods of drug administration are marked. Each vertical line represents a burst or a spike.
Top: Bursts with a silent period less than 100 ms prior to the first
spike in the burst (named HTS); LTS: bursts with a silent period
longer than 100 ms prior to the first spike. The time course in the
change differed between bursts and firing. Especially neuron B
showed a prolonged reduction of bursts.
Fig. 2. Means of the discharge rates of histamine-responsive thalamic
neuronal populations during different conditions showing the blocking effects of histamine receptor antagonists. (A) Effect of the H1
receptor antagonist on the inhibitory action of histamine, (B) effect of
the H2 receptor antagonist on the inhibitory action of histamine, (C)
effect of mepyramine on histamine-activated neurons. Numbers: 1
spontaneous activity, 2 firing rate during administration of the drugs,
3 late response, 4 recovery. * significant change compared with 1, Wt,
P B0.05.
for both nuclear groups (Wt, PB 0.005). The number
of spikes within a burst did not significantly alter. Since
the reduction in firing is caused especially by a reduction in bursting, the fraction of spikes involved in
bursts also was predominantly diminished (Wt, PB
0.005) by histamine. The mean changed from 58.1 to
51% spikes involved in bursts in anterior neurons and
from 47.5 to 35.5% in intralaminar cells. Thus, there is
a significant change to more regular spiking in response
to histamine.
3.3. Effects of histamine on bursting of thalamic
neurons
Burst discharges as shown in Figs. 3 and 4 were
observed in 40 of the 49 anterior and 46 of the 63
intralaminar thalamic neurons. Comparable to the
change in the discharge rate, the number of burst
discharges was significantly decreased (Wt, P B 0.001,
n = 40, means 64.3 bursts per 100 s control to 54.3
during and 50.3 after histamine in the late response
phase for anterior neurons; Wt, P B 0.005, n= 46;
mean 32.4 bursts per 100 s control to 27.8 during and
23.8 after histamine for intralaminar neurons). Although changes in the number of burst discharges
positively correlated with changes in the firing rate,
they can be different in the time course as seen in Figs.
3 and 4. Anterior and intralaminar neurons express
especially bursts after a long silent period that could
possibly follow low-threshold spikes (LTS). The reduction of this type of bursts was shown to be significant
Fig. 4. Bursts and impulses of an anteroventral (A) and a laterodorsal
(B) neuron. Denotations as in Fig. 3. Neuron A formed HTS in a
variable manner. Histamine induced a pronounced reduction of LTS.
N. Sittig, H. Da6idowa / Beha6ioural Brain Research 124 (2001) 137–143
4. Discussion
The predominating effect of histamine on thalamic
neurons consisted in a suppression of the firing rate,
accompanied by a reduction of bursts that were possibly induced by low-threshold Ca++ spikes. The inhibition of firing could be caused by a direct postsynaptic
hyperpolarization or by a reduction of endogenous
depolarizing events. An involvement of activated
GABAergic interneurons can be neglected, since in the
rat only very few interneurons have been observed in
the thalamic nuclei studied in this work [27]. On the
other hand, the reduction of low-threshold bursts and
the change to more regular occurring spikes not involved in bursts has been shown to be the result of
depolarizing effects that inactivate low-threshold Ca++
channels [13,20,21]. Thus, it could be assumed that
more than one transduction mechanisms are involved.
This is also supported by the observation of several
activating effects.
Generally, the action of histamine is mediated by
three receptor subtypes that use various signal transduction mechanisms [11,36]. It seems that H1 as well as
H2 receptors can mediate both suppression and activation of neuronal firing [21,34,35]. H3 receptors function
as presynaptic autoreceptors and suppress the release of
histamine [36]. As heteroreceptors they can also depress
the release of other transmitters [11]. Due to the observed effects of histamine receptor antagonists and
agonists, it is to assume that H1, H2 and H3 receptors
participate in mediating the action of histamine in both
thalamic nuclear groups studied.
In the lateral geniculate nucleus of the thalamus,
slow depolarization induced by histamine and associated with a decrease in a potassium current could be
blocked by H1 receptor antagonists [21]. A further
activating component associated with an increase in
membrane conductance and brought about by stimulation of a hyperpolarization-activated cationic current
could be blocked by the H2 receptor antagonist [21]. In
our investigations on thalamic neurons, the effects of
histamine could also partly be blocked by the H1
receptor antagonist, partly by the H2 receptor antagonist. The predominant reduction in firing was in most
neurons a consequence of the reduction in bursting.
Generally, the main effect of histamine seems to consist
in the change from rhythmic firing to more tonic firing
of thalamic cells mentioned to be important for induction of the waking state [38] and for a faithful transmission of information [21]. On the other hand,
high-frequency groups of action potentials are shown to
be more efficient in releasing transmitters and thus
relaying signals across the synapse than single spikes
[19]. Thus, bursts by themselves may transmit signals
better than single spikes.
141
The modulating effect of histamine on anterior thalamic nuclei that connect limbic structures involved in
processes of learning, memory and reward [46] shows
that activation of the histaminergic system exerts its
role not only through direct action on the hippocampus, but also the thalamic relay.
The reduction in firing especially in the form of
bursts by intralaminar thalamic neurons and activation
of striatal neurons in response to histamine support the
view of the involvement of the drug in regulation of
waking behavior through thalamo-basal-ganglia circuits. Although it has been shown that individual nuclei
of the intralaminar complex regulate functionally segregated basal-ganglia-thalamo-cortical circuits, the intralaminar neurons can modify the level of the entire
basal ganglia system by way of a common input [9], for
instance histamine as shown with our results.
Several brain structures seem to be involved in the
regulatory processes of histamine in sleep and wakefulness. Cortical neurons are reported to be innervated by
the histaminergic fibers [41]. They seem to be activated
by histamine [34], although also depressant effects were
described [10,35]. Histamine influences sleep-generating
mechanisms of the preoptic/anterior hypothalamus [18].
Furthermore, histamine may influence the cortex by
activation of cholinergic neurons of the nucleus basalis
Meynert [14], but also of neurons of the mesopontine
tegmentum that by itself exerts regulatory effects on
thalamo-cortical circuits [17].
In the striatum, only 25% of the varicosities of
histaminergic axons seem to form synaptic contacts of
the asymmetric type [41]. In acutely dissociated striatal
cells, histamine was reported to evoke a net inward
current accompanied by a decrease in the membrane
conductance [25]. Munakata and Akaike [25] concluded
from the study that histamine reduced potassium currents in possibly cholinergic interneurons by means of
H1 and H2 receptors. It is known that striatal cholinergic interneurons receive especially an input from the
parafascicular thalamic nucleus [16]. Although these
interneurons represent only about 2% of the neuronal
population [16], they are possibly easy to detect by a
recording electrode due to their large size and the
higher spontaneous activity in comparison to projection
neurons. In anesthetized animals they have a tonic
firing frequency between 2 and 10 spikes per s [49].
Since we also observed effects of histamine in very
slowly firing cells, and projection cells form about 95%
of the population, we would assume that histamine is
also able to affect projection neurons. Naturally, indirect effects mediated by different interneurons located
in the near vicinity have to be taken into account. Due
to the action of histamine on cholinergic neurons,
interactions with acetylcholine have to be considered.
Acetylcholine has been shown to interact with other
transmitter systems [5,7,15] and to stabilize the potentials of striatal cells [15].
142
N. Sittig, H. Da6idowa / Beha6ioural Brain Research 124 (2001) 137–143
Furthermore, interactions of histamine with the dopaminergic system can be involved [26]. In the rat
striatum, the synthesis of dopamine can be inhibited by
H3 receptor activation [23]. The dopamine level seems
to be reduced by histamine also via the H1 receptor [8].
Thus, the modulatory action of dopamine on striatal
neurons [7,15] may be changed also by histamine.
Striatal projection neurons are often silent in anesthetized rats [5,48]. Due to the existence of various
potassium conductances their membrane polarization
can spontaneously vary between two states [48]. Since
histamine mainly activates striatal neurons, it might
promote the transition to the more depolarized ‘up’
state [48]. Thus, histamine has to be included into the
transmitter systems modulating the activity of the neostriatum [2,7].
Acknowledgements
The authors would like to thank Ursula Seider and
Roland Schneider for expert technical assistance. They
express their gratitude to Prof. J.P. Huston for encouragement of the study.
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
References
[1] Brown RE, Fedorov NB, Haas HL, Reymann KG. Histaminergic modulation of synaptic plasticity in area CA1 of rat
hippocampal slices. Neuropharmacology 1995;34:181 – 90.
[2] Calabresi P, De Murtas M, Bernardi G. The neostriatum beyond
the motor function: experimental and clinical evidence. Neuroscience 1997;78:39 – 60.
[3] Chiavegatto S, Nasello AG, Bernardi MM. Histamine and spontaneous motor activity: biphasic changes, receptors involved and
participation of the striatal dopamine system. Life Sci
1998;62:1875 – 88.
[4] Davidowa H, Albrecht D, Gabriel H-J, Zippel U. Cholecystokinin affects the neuronal discharge mode in the rat lateral
geniculate body. Brain Res Bull 1995;36:533 –7.
[5] Davidowa H, Wetzel K, Vierig G. Effects of cholecystokinin
agonists on striatal neurons are reduced by acetylcholine. Peptides 1997;18:541 –5.
[6] Deschênes M, Bourassa J, Parent A. Striatal and cortical projections of single neurons from the central lateral thalamic nucleus
in the rat. Neuroscience 1996;72:679 – 87.
[7] Di Chiara G, Morelli M, Consolo S. Modulatory functions of
neurotransmitters in the striatum: ACh/dopamine/NMDA interactions. Trends Neurosci 1994;17:228 –33.
[8] Dringenberg HC, de Souza-Silva MA, Schwarting RK, Huston
JP. Increased levels of extracellular dopamine in neostriatum and
nucleus accumbens after histamine H1 receptor blockade.
Naunyn Schmiedebergs Arch Pharmacol 1998;358:423 – 9.
[9] Groenewegen HJ, Berendse HW. The specificity of the ‘nonspecific’ midline and intralaminar thalamic nuclei. Trends Neurosci
1994;17:52 – 7.
[10] Haas H, Wolf P. Central actions of histamine: microelectrophorectic studies. Brain Res 1977;122:269 – 79.
[11] Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley
NP, Young JM, Schunack W, Levi R, Haas HL. International
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev 1997;49:253 – 78.
Huston JP, Wagner U, Hasenöhrl RU. The tuberomammillary
nucleus projections in the control of learning, memory and
reinforcement process: evidence for an inhibitory role. Behav
Brain Res 1997;83:97 – 105.
Jahnsen H, Llinas R. Ionic basis for the electro-responsiveness
and oscillatory properties of guinea-pig thalamic neurones in
vitro. J Physiol London 1984;349:227 – 47.
Khateb A, Fort P, Pegna A, Jones BE, Mühlethaler M. Cholinergic nucleus basalis neurons are excited by histamine in vitro.
Neuroscience 1995;69:495 – 506.
Kitai ST, Surmeier DJ. Cholinergic and dopaminergic modulation of potassium conductances in neostriatal neurons. Adv
Neurol 1993;60:40 – 52.
Lapper SR, Bolam JP. Input from the frontal cortex and the
parafascicular nucleus to cholinergic interneurons in the dorsal
striatum of the rat. Neuroscience 1992;51:533 – 45.
Lin JS, Hou Y, Sakai K, Jouvet M. Histaminergic descending
inputs to the mesopontine tegmentum and their role in the
control of cortical activation and wakefulness in the cat. J
Neurosci 1996;16:1523 – 37.
Lin JS, Sakai K, Jouvet M. Hypothalamo-preoptic histaminergic
projections in sleep-wake control in the cat. Eur J Neurosci
1994;6:618 – 25.
Lisman JE. Bursts as a unit of neuronal information: making
unreliable synapses reliable. Trends Neurosci 1997;20:38 –43.
Lo FS, Lu S-M, Sherman SM. Intracellular and extracellular in
vivo recording of different response modes for relay cells of the
cat’s lateral geniculate nucleus. Exp Brain Res 1991;83:317 –28.
McCormick DA, Williamson A. Modulation of neuronal firing
mode in cat and guinea pig LGNd by histamine: possible cellular
mechanisms of histaminergic control of arousal. J Neurosci
1991;11:3188 – 99.
Mochizuki T, Yamatodani A, Okakura K, Horii A, Inagaki N,
Wada H. Circadian rhythm of histamine release from the hypothalamus of freely moving rats. Physiol Behav 1991;51:391 –4.
Molina-Hernandez A, Nunez A, Arias-Montano JA. Histamine
H3-receptor activation inhibits dopamine synthesis in rat striatum. Neuroreport 2000;17:163 – 6.
Monti JM. Involvement of histamine in the control of the
waking state. Life Sci 1993;53:1331 – 8.
Munakata M, Akaike N. Regulation of K + conductance by
histamine H1 and H2 receptors in neurones dissociated from rat
neostriatum. J Physiol London 1994;480:233 – 45.
Nowak JZ, Pilc A. Direct or indirect action of histamine on
dopamine metabolism in the rat striatum? Eur J Pharmacol
1977;46:171 – 5.
Ottersen OP, Storm-Mathisen J. GABA-containing neurons in
the thalamus and pretectum of the rodent. An immunocytochemical study. Anat Embryol 1984;170:197 – 207.
Palacios JM, Wamsley JK, Kuhar MJ. The distribution of
histamine H1-receptors in the rat brain: an autoradiographic
study. Neuroscience 1981;6:15 – 37.
Panula P, Pirvola U, Auvinen S, Airaksinen MS. Histamine-immunoreactive nerve fibers in the rat brain. Neuroscience
1989;28:585 – 610.
Paxinos G. The Rat Nervous System, second ed. San Diego:
Academic Press, 1995:366.
Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates, second ed. San Diego: Academic Press, 1986.
Pollard H, Moreau J, Arrang JM, Schwartz JC. A detailed
mapping of histamine H3 receptors in rat brain areas. Neuroscience 1993;52:169 – 89.
Prast H, Argyriou A, Philippu A. Histaminergic neurons facilitate social memory in rats. Brain Res 1996;734:316 – 8.
N. Sittig, H. Da6idowa / Beha6ioural Brain Research 124 (2001) 137–143
[34] Reiner PB, Kamondi A. Mechanisms of antihistamine-induced
sedation in the human brain: H1 receptor activation reduces a
background
leakage
potassium
current.
Neuroscience
1994;59:579 – 88.
[35] Sastry BSR, Phillis JW. Depression of rat cerebral cortical
neurones by H1 and H2 histamine receptor agonists. Eur J
Pharmacol 1976;38:269 –73.
[36] Schwartz J-C, Arrang J-M, Garbarg M, Korner M. Properties
and roles of three subclasses of histamine receptors in brain. J
Exp Biol 1986;124:203 –24.
[37] Stehle J. Effects of histamine on spontaneous electrical activity
of neurons in rat suprachiasmatic nucleus. Neusci Lett
1991;130:217 – 20.
[38] Steriade M. Mechanisms underlying cortical activation: neuronal
organization and properties of the midbrain reticular and intralaminar thalamic nuclei. In: Pompeiano O, Marsan A, editors.
Brain Mechanisms and Perceptual Awareness. New York: Raven
Press, 1981:327 – 77.
[39] Steriade M, Deschênes M. The thalamus as a neuronal oscillator. Brain Res Rev 1984;8:1 –63.
[40] Steriade M, Jones EG, McCormick DA, editors. Thalamus:
Organisation and Function, vol. I. Amsterdam: Elsevier,
1997:35 – 43.
[41] Takagi H, Morishima Y, Matsuayma T, Hayashi H, Watanabe
T, Wada H. Histaminergic axons in the neostriatum and cerebral
cortex of the rat: a correlated light and electron microscopic
immunocytochemical study using histidine decarboxylase as a
marker. Brain Res 1986;364:114 –23.
143
[42] Tasaka K. New Advances in Histamine Research. Tokyo:
Springer, 1994:1 – 68.
[43] Uteshev V, Stevens DR, Haas HL. A persistent sodium current
in acutely isolated histaminergic neurons from rat hypothalamus.
Neuroscience 1995;66:143 – 9.
[44] Vorobjew VS, Sharonova IN, Walsh IB, Haas HL. Histamine
potentiates N-methyl-D-aspartate responses in acutely isolated
hippocampal neurons. Neuron 1993;11:837 – 44.
[45] Wada H, Inagaki N, Yamatodani A, Watanabe T. Is the histaminergic neuron system a regulatory center for whole-brain
activity? Trends Neurosci 1991;14:415 – 8.
[46] Warburton EC, Aggleton JP. Differential deficits in the Morris
water maze following cytotoxic lesions of the anterior thalamus
and fornix transection. Behav Brain Res 1999;98:27 – 38.
[47] Watanabe T, Taguchi Y, Shiosaka S, Tanaka J, Kubota H,
Terano Y, Tohyama M, Wada H. Distribution of the histaminergic neuron system in the central nervous system of rats; a
fluorescent immunohistochemical analysis with histidine decarboxylase as a marker. Brain Res 1984;295:13 – 25.
[48] Wilson CJ, Kawaguchi Y. The origins of two-state spontaneous
membrane potential fluctuations of neostriatal spiny neurons. J
Neurosci 1996;16:2397 – 410.
[49] Wilson CJ, Chang HT, Kitai ST. Firing patterns and synaptic
potentials of identified giant aspiny interneurons in the rat
neostriatum. J Neurosci 1990;10:508 – 19.
[50] Zimmermann P, Privou C, Huston JP. Differential sensitivity of
the caudal and rostral nucleus accumbens to the rewarding
effects of a H1-histaminergic receptor blocker as measured with
place-preference and self-stimulation behavior. Neuroscience
1999;94:93 – 103.