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PubMed1996

A model of multiplicative neural responses in parietal cortex.

Visual responses of neurons in parietal area 7a are modulated by a combined eye and head position signal in a multiplicative manner. Neurons with multiplicative responses can act as powerful computational elements in neural networks. In the case of parietal cortex, multiplicative gain modulation appears to play a crucial role in the transformation of object locations from retinal to body-centered coordinates. It has proven difficult to uncover single-neuron mechanisms that account for neuronal multiplication. Here we show that multiplicative responses can arise in a network model through population effects. Specifically, neurons in a recurrently connected network with excitatory connections between similarly tuned neurons and inhibitory connections between differently tuned neurons can perform a product operation on additive synaptic inputs. The results suggest that parietal responses may be based on this architecture.

Animals↗
PubMed1995

Subplate neurons and the patterning of thalamocortial connections.

The patterning of the cerebral cortex into functionally distinct domains relies on the formation of appropriate connections between the thalamus and the cortex during development. To identify the mechanisms that underlie cortical target selection by thalamic axons, we have examined the role of cellular interactions in the formation of connections between the lateral geniculate nucleus (LGN) and the visual cortex during development of the cat visual system. The morphology of LGN axons as they grow towards the visual cortex suggests that interactions within the subplate zone may be important in the development of geniculocortical connections. The requirement for subplate neurons in this process was examined by ablating subplate neurons underlying the visual cortex at various developmental stages. When subplate cells are deleted between E38 and E42, prior to target innervation by LGN axons, these axons fail to select the visual cortex as their correct target and instead grow past it, staying restricted to the white matter. Deletion of subplate cells at later stages, between P2 and P7, does not affect target selection, but instead it prevents the segregation of LGN axons into ocular dominance columns within layer IV of the cortex. The effects of subplate neuron ablation suggest that interactions between thalamic axons and subplate cells are of critical importance in the specification of thalamocortical connections during development.

Animals↗
PubMed1987

Physiological studies of brainstem reticular connectivity. II. Responses of mPRF neurons to stimulation of mesencephalic and contralateral pontine reticular formation.

The connectivity between medial pontine reticular formation (mPRF) and the contralateral mPRF and between mPRF and the mesencephalic reticular formation (MRF) was studied by intracellular recordings of mPRF neuronal responses to microstimulation of the contralateral gigantocellular field (cFTG) portion of mPRF and ipsilateral MRF in unanesthetized, undrugged cats. There was a very high percentage (75-86%) of monosynaptic latency postsynaptic potentials (PSPs) in mPRF neurons in response to microstimulation of cFTG and MRF, and most PSPs (72-82%) were excitatory ones (EPSPs). The initial EPSPs from cFTG stimulation were characterized by a rapid rise time and a relatively constant latency, while those from MRF had a less rapid rise time and a longer plateau; EPSPs from both sites frequently led to spike potential generation. In contrast, the percentage of initial monosynaptic inhibitory PSPs (EPSPs) was less than 4% from each of these regions, statistically significantly less than that from bulbar FTM and bulbar FTG stimulation (about 12%) reported in the companion paper. Injection of depolarizing current in mPRF neurons unmasked hyperpolarizing PSP responses to stimulation that followed initial depolarizing PSPs. Intracellular HRP labeling indicated that these data were from recordings from neurons with 20-100 microns diameters, with 80% greater than 40 microns. Neurons with a different discharge pattern for this area of the pons, a stereotyped burst pattern, were recorded just ventral to mPRF; this discharge pattern resembled that found in inhibitory interneurons in other central nervous system regions. There were no differences in the density and pattern of orthodromic PSPs between those mPRF neurons that were antidromically activated from cFTG and the general population that was not antidromically activated from cFTG or other stimulated sites; this suggests, when combined with data of the companion paper, an identity of input and output elements in mPRF with respect to synaptic response properties. The high degree of connectivity between reticular regions may furnish a substrate for functional interaction.

Animals↗
PubMed1991

Shared-stimulus driving and connectivity in groups of neurons in the dorsal cochlear nucleus.

Extracellular spike discharges were recorded from ensembles of up to five neurons simultaneously in the DCN of guinea pig using solid-state, thin-film, multichannel electrodes having up to five recording sites spanning up to 600 microns. Responses from 73 unit pairs were collected of which 54 had both units responding to pseudorandom wideband noise stimulation. Shared-stimulus driving was present in 78% (42/54) of the unit pairs and could be attributed to an overlap in their spectral sensitivities. Effective connectivity was indicated for 87% (47/54) of the unit pairs. Wideband noise proved more useful than tonebursts for investigating shared-stimulus driving and connectivity because it evoked widespread, but not overly synchronous, responses in the ensembles.

Acoustic Stimulation↗
PubMed1997

LTP and spatial learning--where to next?

Hebb suggested, in 1949, that memories could be stored by forming associative connections between neurons if the criterion for increasing the connection strength between them be that they were active simultaneously. Much attention has been devoted towards trying to determine a) if there is a physiological substrate of such a rule, and b) if so, whether the phenomenon participates in real-life memory formation. The discovery of the electrically induced increase in synaptic strength known as long-term potentiation (LTP), in the early 1970s, demonstrated that a neural version of the Hebb rule could be observed under laboratory conditions in the hippocampus, a structure important for some types of learning. However, a quarter of a century later, the evidence linking LTP to learning and memory is still contradictory. The purpose of the present article is to review and assess the types of approach that have been taken in trying to determine whether hippocampal synaptic plasticity participates in memory formation.

Animals↗
PubMed2005

Neurogenesis and neuronal communication on micropatterned neurochips.

Neural networks are formed by accurate connectivity of neurons and glial cells in the brain. These networks employ a three-dimensional bio-surface that both assigns precise coordinates to cells during development and facilitates their connectivity and functionality throughout life. Using specific topographic and chemical features, we have taken steps towards the development of poly(dimethylsiloxane; PDMS) neurochips that can be used to generate and study synthetic neural networks. These neurochips have micropatterned structures that permit adequate cell positioning and support cell survival. Within days of plating, cells differentiate into neurons displaying excitability and communication, as evidenced by intracellular calcium oscillations and action potentials. The structural and functional capacities of such simple neural networks open up new opportunities to study synaptic communication and plasticity.

Action Potentials↗
PubMed1980

Naturally occurring neuron death in the optic layers of superior colliculus of the postnatal rat.

Application of light and electron microscopic techniques to the superior colliculus of the normal rat shows that a number of neurons die within the first week after birth. Cells in the earliest recognizable stages of degeneration are characterized by an overall increase in electron density and dilation of the intracellular cisternae, although there are only minimal changes in the chromatin pattern of the nucleus. Synapses are found on these cells. A second type of degenerating cell, with more striking changes in the nucleus, also appears in the tissue but very infrequently. In later stages of degeneration, cells are reduced to a condensed chromatin mass surrounded by disrupted fragments of the rest of the cell. This 'cellular debris' is found within glial cytoplasm. The majority of these debris profiles appear in the first postnatal week and are usually most abundant in the caudal third compared to either the rostral or middle thirds of the colliculus. The results suggest that the mechanisms controlling neuron number in the superior colliculus are operative in the postnatal rat but argue against a simple relationship between the survival of a particular neuron and the total number of optic connections that neuron has received.

Animals↗
PubMed1990

Peripheral nerve pathways to neurons in the guinea pig inferior mesenteric ganglion determined electrophysiologically after chronic nerve section.

Peripheral synaptic pathways to neurons in the guinea pig inferior mesenteric ganglion (IMG) were studied. Nerve trunks innervating neurons in the ganglion were surgically sectioned and intracellular electrical responses to nerve stimulation were measured 6-8 days after surgery. In all animals ganglia were decentralized by removal of the lumbar sympathetic chain ganglia L2 through L4 and in addition two peripheral nerves were sectioned leaving the ganglion innervated by only one peripheral nerve. Fast and slow excitatory postsynaptic potential (EPSP) were evoked with electrical stimulation of each of the nerve trunks and with distension of the colon. The thresholds to evoke fast EPSPs and the amplitude of slow EPSPs were compared for each nerve trunk among the different surgical groups including sham-operated controls and completely denervated ganglia. Both fast and slow EPSPs could be evoked electrically from each intact peripheral nerve trunk after the other three nerve trunks had been sectioned, which demonstrates that nerve fibers with cell bodies in the regions innervated by the peripheral nerves make functional synaptic connections with neurons in the inferior mesenteric ganglion. In general, nerve sections increased the threshold for evoking fast EPSPs and decreased the amplitude of electrically-evoked slow EPSPs compared to control ganglia. Synaptic potentials could also be evoked with stimulation of cut nerve trunks, demonstrating that branches of nerve fibers from peripheral nerves enter other nerve trunks. The hypogastric nerve was unique in that branches of axons eliciting fast but not slow synaptic potentials in the ganglion entered this nerve trunk. Distension-induced fast and slow EPSPs were present only if the lumbar colonic nerve was intact and they were not altered by section of the other nerve trunks. In contrast, the slow EPSPs evoked with electrical stimulation of the lumbar colonic nerve were significantly smaller when at least one other nerve trunk was sectioned suggesting that the axon branches from other nerve trunks which enter the lumbar colonic nerve are not activated by distension. These studies demonstrate that neurons eliciting either fast or slow synaptic potentials with cell bodies in regions innervated by the peripheral nerve trunks make functional synaptic connections with neurons of the inferior mesenteric ganglion. The results also suggest that the majority of mechanosensory neurons mediating excitatory synaptic responses to colon distension are neurons with a peripheral cell body.

Action Potentials↗
PubMed2003

ACh and ATP mediate excitatory transmission in cat carotid identified chemoreceptor units in vitro.

Several molecules have been proposed as excitatory transmitters between glomus (type 1) cells and nerve terminals of petrosal ganglion (PG) neurons in the carotid body (CB). We tested whether ACh and ATP have a role to play as excitatory transmitters in the cat CB by recording intracellularly from identified PG neurons functionally connected to the CB in vitro. PG neurons projecting to the CB were classified according to their intracellular responses as: (a) neurons with humped action potentials (hAP neurons) responding phasically to long-lasting depolarizing pulses (53/67), and (b) neurons with smooth action potentials (non-hAP neurons) that fire tonically during long-lasting depolarizations (14/67). CB stimulation by stop flow and/or acidosis induced activity in 28 of 39 hAP-type neurons, being classified as chemosensory, but in none of the non-hAP neurons. Hexamethonium (10 microM) and suramin (100 microM) reversibly abolished the increased discharges evoked in chemosensory neurons (8/9) by stop flow or acidosis. Moreover, 24 of 27 chemosensory neurons responded to ganglionar application of ACh and ATP, while two neurons responded only to ACh and one to ATP. Mechanical deformation of the carotid sinus induced firing activity in 10 of 13 non-hAP neurons, but in none of the hAP neurons tested. Interestingly, 4/10 non-hAP neurons, which responded to carotid sinus mechanical stimulation also responded to ganglionar application of ATP, but were insensitive to ACh. Present results favor the hypothesis that ACh and ATP are excitatory transmitters in the cat CB, acting-at least-on the PG neuron terminals in the CB.

Acetylcholine↗
PubMed1999

Genesis and role of coordinated firing in a feedforward network: a model study of the enteric nervous system.

The enteric nervous system can generate complex motor patterns independently of the central nervous system. The ascending enteric reflex pathway consists of sensory neurons, long chains of a single class of orally directed interneuron and excitatory motor neurons. Because of the importance of this pathway in peristalsis, it was modelled from the firing of sensory neurons through to muscle membrane activation. The model was anatomically realistic in the number of neurons simulated and in the patterns of connections between neurons. The model was also realistic in the simulation of ligand-gated currents in neuron and muscle membrane, current flow in the muscle syncytium and voltage-dependent currents in muscle. Sensory neurons were activated in a manner consistent with a brief mechanical stimulus. Transmission between sensory neurons and first-order interneurons was by slow excitatory transmission, which caused interneurons to fire continuously for several hundred milliseconds. Interneurons then transmitted to higher order interneurons by fast excitatory postsynaptic potentials, each lasting for around 40 ms. As the activity propagated along the pathway, random firing became progressively more synchronized between neurons, until the network as a whole was firing in a coordinated manner. The coordinated firing was a robust phenomenon over a wide range of network and neuron parameters. It is therefore possible that this is a general property of feedforward networks that receive high levels of sustained input. The smooth muscle model indicated that bursting input to the muscle may increase the likelihood of muscle cells firing action potentials when compared with uniform input. In addition, the syncytium model explains how the predicted muscle excitation might be related to current experimental observations.

Action Potentials↗
PubMed1999

Fine structure, synaptology and immunocytochemistry of large neurons in the rat dorsal cochlear nucleus connected to the inferior colliculus.

Neurons in the rat dorsal cochlear nucleus that project to the inferior colliculus (pyramidal and giant) were retrograde labelled with wheat germ agglutinin conjugated to horseradish peroxydase. Both cell types showed a similar ultrastructural feature, particularly the rough endoplasmic reticulum was well developed and sometimes surrounded the nucleus. The synaptological profile was similar in pyramidal and giant cells. Axo-somatic terminals covered 40-70% of the perimeter of pyramidal cells and 35-60% of the perimeter of giant neurons. Giant neurons featured bipolar or multipolar shape and different orientation but they possessed a similar synaptic profile. Most axo-somatic terminals contained flat and pleomorphic synaptic vesicles, some pleomorphic vesicles. Few terminals contained round vesicles. These cells were consistently immuno-negative for both glycine and GABA and variably positive for glutamate. The immunoelectron microcopic study of thin sections showed that glycine immunoreactivity was constantly present in terminals enriched with flat vesicles, which often did not show GABA immunoreactivity. Few anterograde labelled boutons containing flat vesicles were in contact with the proximal dendrites and the cell bodies of pyramidal and giant neurons. The origin of these terminals is discussed. No other cells of the dorsal cochlear nucleus, in particular cartwheel and tuberculo-ventral neurons, were in contact with labelled boutons. The present results suggest that descending inhibitory collicular projections are essentially directed to the large excitatory neurons of the dorsal cochlear nucleus.

Animals↗
PubMed1992

Pharmacological characterization of calcium currents and synaptic transmission between thalamic neurons in vitro.

We recorded from pairs of cultured, synaptically connected thalamic neurons. Evoked excitatory postsynaptic currents (EPSCs) reversed at +17 mV and were blocked reversibly by 1 mM kynurenic acid, a glutamate receptor antagonist. NMDA and non-NMDA receptors mediated excitatory post-synaptic responses, as shown by selective block of EPSC components with 50 microM (+/-)-2-amino-5-phosphonopentanoic acid and 10 microM 6,7-dinitroquinoxaline-2,3-dione, respectively. Inhibitory postsynaptic responses were evoked less frequently and were blocked by the GABAA receptor antagonist (-)-bicuculline methochloride. The pharmacological profiles of whole-cell calcium currents and evoked EPSCs were compared. With 50 microM cadmium chloride (Cd), whole-cell low voltage-activated (LVA) calcium currents were reduced in amplitude and high voltage-activated (HVA) calcium currents and excitatory synaptic transmission were completely blocked. This suggests that the residual calcium influx through LVA channels into the presynaptic terminal does not suffice to trigger transmitter release. A saturating concentration of omega-conotoxin GVIA (omega-CgTx) (2.5 microM) blocked one-third of whole-cell HVA calcium currents and evoked EPSCs. The dihydropyridine nifedipine (50 microM) reversibly reduced whole-cell HVA calcium currents in a voltage-dependent manner but not excitatory synaptic transmission. Cd and omega-CgTx did not alter amplitude distributions of miniature EPSCs, demonstrating that the inhibition of synaptic transmission was due to block of presynaptic calcium channels. We conclude that excitatory glutamatergic transmission in thalamic neurons in vitro was mediated mainly by HVA calcium currents, which were insensitive to omega-CgTx and nifedipine.

Animals↗
PubMed1998

Anatomical evidence for a mechanism of lateral inhibition in the rat thalamus.

The aim of this study was to determine whether or not thalamic reticular nucleus (Rt) neurons form synaptic connections with the thalamocortical (TC) neurons from which they receive synaptic contacts. Therefore, we examined, in adult rats, the relationships between single TC and Rt neurons, which had been marked simultaneously with an anterograde/retrograde tracer (biocytin or Neurobiotin), using the extracellular or juxtacellular technique. (i) From 30 successful extracellular microapplications of marker into the Rt, 22 gave retrogradely marked TC somatodendritic arbors at the fringe of or clear outside the anterogradely darkly stained Rt axon terminal fields. Following biocytin application into the thalamus, few cells were retrogradely stained in the Rt at the periphery of the anterogradely labelled axon terminal field. (ii) The juxtacellular filling of a single Rt cell was accompanied by the back-filling of a single TC neuron (n = 4 pairs), which presumably formed synaptic contacts with the former cell. The somatodendritic complex of the back-filled TC neuron was located outside the Rt cell's axonal arbor. These anatomical data provide clear evidence that Rt and thalamic neurons predominantly form between themselves open rather than closed loop connections. Because TC neurons make glutamatergic synapses onto Rt cells, which are GABAergic, and are the first elements synaptically activated by prethalamic afferents into the TC-Rt network, the present results strongly support the hypothesis that Rt neurons principally generate a mechanism of lateral inhibition in the thalamus.

Animals↗
PubMedDate not supplied

Estradiol and progesterone regulate neuronal structure and synaptic connectivity in adult as well as developing brain.

Until recently, it has been widely believed that the adult brain does not undergo changes in its structure, particularly in relation to the actions of circulating hormones. It has now become clear that estradiol and progesterone have important effects on adult brain structure and function. Single section Golgi silver staining and electron microscopy have been used to analyze numbers of spines on dendrites and to count synapses on dendritic spines. In the adult female rat brain, we find that dendrites of neurons in the ventromedial hypothalamus and CA1 region of the hippocampus sprout increased numbers of spines on dendrites and then lose them during the 4- or 5-day estrous cycle. Increased spine numbers are accompanied by increased numbers of synapses on spines. In the hippocampus, the loss of spines and spine synapses occurs during a 24-h period between the time of maximum sexual receptivity on the day of proestrus and the next day, the day of estrus. This loss is not due solely to the decline in estradiol; however, giving progesterone speeds up the decline, and administering the antiprogestin, Ru486, on proestrus blocks the natural decline of synapse density. The changes of synaptic density in the hypothalamus are responsible, at least in part, for the cyclicity of sexual behavior, whereas the cyclicity of synapses in the hippocampus may subserve functions related to spatial learning and memory. In human subjects, cyclic fluctuations in gonadal hormones are associated with cyclic changes in performance on a variety of cognitive and motor tasks.

Animals↗
PubMed1997

A network of tufted layer 5 pyramidal neurons.

Tufted layer 5 (TL5) pyramidal neurons are important projection neurons from the cerebral cortex to subcortical areas. Recent and ongoing experiments aimed at understanding the computational analysis performed by a network of synaptically connected TL5 neurons are reviewed here. The experiments employed dual and triple whole-cell patch clamp recordings from visually identified and preselected neurons in brain slices of somatosensory cortex of young (14- to 16-day-old) rats. These studies suggest that a local network of TL5 neurons within a cortical module of diameter 300 microns consists of a few hundred neurons that are extensively inter-connected with reciprocal feedback from at least first-, second- and third-order target neurons. A statistical analysis of synaptic innervation suggests that this recurrent network is not randomly arranged and hence each neuron could be functionally unique. Synaptic transmission between these neurons is characterized by use-dependent synaptic depression which confers novel properties to this recurrent network of neurons. First, a range of rates of depression for different synaptic connections enable each TL5 neuron to receive a unique mixture of information about the average firing rates and the temporally correlated action potential (AP) activity in the population of presynaptic TL5 neurons. Second, each AP generated by any neuron in the network induces a change (defined as an iteration step) in the functional coupling of the neurons in the network (defined as network configuration). It is proposed that the network configuration is iterated during a stimulus to achieve an optimally orchestrated network response. Hebbian, anti-Hebbian and neuromodulatory-induced modifications of neurotransmitter release probability change the rates of synaptic depression and thereby alter the iteration step size. These data may be important to understand the dynamics of electrical activity within the network.

Animals↗
PubMed1976

[Connections between inspiratory medullary neurons and phrenic or intercostal motoneurones (author's transl)].

10 The activity of 107 medullary inspiratory neurones has been recorded extracellularly in anesthetized cats (urethane-chloralose). According to their localization in the medulla and to their axonal pathways (tested by antidromic activation), these neurones were classified as: bulbo-spinal neurones (NBSI) which send their axons to the spinal cord; they are located in the dorsal or the ventral respiratory nucleus; propriobulbar neurons (NPBI) whose axons are probably entirely located within the medulla; they are found only in the ventral nucleus. 20 Summation of gross discharges from phrenic (C5 ventral root) or inspiratory intercostal (from T4 to T10) nerves was triggered by spikes from medullary respiratory neurones. If the studied neurone controls the activity of the recorded motor fibres, after sommation of a great number of sweeps (3,000 to 5,000), the summed nerve activity displays a short delay excitatory wave, indicating that the activity of the motoneurones is increased after the onset of the medullary potential. On the other hand, there is a flat summed nerve activity if the nerve discharge is not directly dependent on the medullary recorded activity. 30 The dorsal nucleus NBSIs send their axon to the contralateral phrenic motoneurones (as it is revealed by the excitatory wave noted on the summed phrenic nerve activity, fig. 1 and 4) and not to the intercostal motoneurones (fig. 4). 40 The ventral nucleus NBSIs control contralateral intercostal motoneurones (fig. 5). Some of them send their axons only to these motoneurones, but the majority also act on phrenic motoneurones (fig. 2 and 5). 50 Connections between NBSIs and phrenic motoneurones are monosynaptic and probably also those between NBSIs and intercostal motoneurones. 60 No excitatory wave has been observed on phrenic or intercostal summed activity when summation was triggered by NPBI spikes (fig. 3). This confirms the accuracy of the "antidromic stimulation test" used to classify medullary respiratory neurons.

Animals↗
PubMed2005

Globus pallidus neurons dynamically regulate the activity pattern of subthalamic nucleus neurons through the frequency-dependent activation of postsynaptic GABAA and GABAB receptors.

Reciprocally connected GABAergic neurons of the globus pallidus (GP) and glutamatergic neurons of the subthalamic nucleus (STN) are a putative generator of pathological rhythmic burst firing in Parkinson's disease (PD). Burst firing of STN neurons may be driven by rebound depolarization after barrages of GABA(A) receptor (GABA(A)R)-mediated IPSPs arising from pallidal fibers. To determine the conditions under which pallidosubthalamic transmission activates these and other postsynaptic GABARs, a parasagittal mouse brain slice preparation was developed in which pallidosubthalamic connections were preserved. Intact connectivity was first confirmed through the injection of a neuronal tracer into the GP. Voltage-clamp and gramicidin-based perforated-patch current-clamp recordings were then used to study the relative influences of GABA(A)R- and GABA(B)R-mediated pallidosubthalamic transmission on STN neurons. Spontaneous phasic, but not tonic, activation of postsynaptic GABA(A)Rs reduced the frequency and disrupted the rhythmicity of autonomous firing in STN neurons. However, postsynaptic GABA(B)Rs were only sufficiently activated to impact STN firing when pallidosubthalamic transmission was elevated or pallidal fibers were synchronously activated by electrical stimulation. In a subset of neurons, rebound burst depolarizations followed high-frequency, synchronous stimulation of pallidosubthalamic fibers. Although GABA(B)R-mediated hyperpolarization was itself sufficient to generate rebound bursts, coincident activation of postsynaptic GABA(A)Rs produced longer and more intense burst firing. These findings elucidate a novel route through which burst activity can be generated in the STN, and suggest that GABARs on STN neurons could act in a synergistic manner to generate abnormal burst activity in PD.

2-Amino-5-phosphonovalerate↗
PubMed1995

Direct projection from the suprachiasmatic nucleus to hypophysiotrophic corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus of the hypothalamus demonstrated by means of Phaseolus vulgaris-leucoagglutinin tract tracing.

The diurnal rhythm of the activity of the hypothalamo-pituitary-adrenal axis is generated by the circadian pacemaker located in the suprachiasmatic nuclei (SCN). However, the neuronal circuit connecting the SCN with the neurosecretory corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus is not clear. To investigate the existence of a direct link between the SCN and the CRF neurons in the PVN we combined microiontopheretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the SCN with immunohistochemical detection of CRF in adrenalectomized male rats. The majority of the PHA-L-ir axons originating from the SCN terminated in the subparaventricular area. A minor contingent of fibers continued into the PVN proper, involving the medial and dorsal parvicellular subnuclei of the PVN. All PHA-L injections involving the entire SCN gave rise to PHA-L positive fibers endowed with boutons en passage and terminal boutons contacting CRF positive cell bodies in the PVN. Notably, varicosities on the PHA-L labelled fibers were present in close proximity to cell bodies and proximal dendrites of a subportion of the CRF neurons located in the periphery of the CRF cell cluster. The present study provides the first evidence to suggest a direct connection between the SCN and the CRF producing neurons of the hypothalamo-pituitary-adrenocortical axis in the PVN. Considering the sparse number of PHA-L-ir varicosities in close proximity to the CRF-ir cells, it seems likely that this direct pathway constitutes but a part of a projection system from the SCN, possibly involving multisynaptic pathways, influencing the hypothalamo-pituitary-adrenocortical axis.

Animals↗