Synapse and Its Classification

import requests
import os
from io import BytesIO
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, Image as RLImage, KeepTogether
)
from reportlab.lib.pagesizes import A4
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.lib import colors
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import PageBreak

OUTPUT = "/home/daytona/workspace/synapse-pdf/Synapse_Classification.pdf"

# ── Download images ──────────────────────────────────────────────────────────
IMG_URLS = {
    "anatomical": "https://cdn.orris.care/cdss_images/19769af8652d4cdcc2a503ea5e8ea86c7a0ea8f621c4fd39abf7ac476ae7c0b8.png",
    "elec_chem":  "https://cdn.orris.care/cdss_images/504ae477f587824fab304dce8fa05afc8f79d41006508d9203ebf92a707b8185.png",
}

def fetch_img(url, name):
    path = f"/home/daytona/workspace/synapse-pdf/{name}.png"
    if not os.path.exists(path):
        r = requests.get(url, timeout=20)
        with open(path, "wb") as f:
            f.write(r.content)
    return path

img_paths = {k: fetch_img(v, k) for k, v in IMG_URLS.items()}

# ── Styles ───────────────────────────────────────────────────────────────────
W, H = A4
styles = getSampleStyleSheet()

BLUE   = colors.HexColor("#1a3a5c")
LBLUE  = colors.HexColor("#2e6da4")
TEAL   = colors.HexColor("#17a589")
LTEAL  = colors.HexColor("#d0f0eb")
LGREY  = colors.HexColor("#f4f6f8")
DGREY  = colors.HexColor("#5d6d7e")
WHITE  = colors.white
ACCENT = colors.HexColor("#e8f4fd")

title_style = ParagraphStyle("Title", parent=styles["Normal"],
    fontSize=26, textColor=WHITE, fontName="Helvetica-Bold",
    alignment=TA_CENTER, spaceAfter=4)

subtitle_style = ParagraphStyle("Subtitle", parent=styles["Normal"],
    fontSize=13, textColor=colors.HexColor("#d6eaf8"),
    fontName="Helvetica", alignment=TA_CENTER, spaceAfter=0)

h1 = ParagraphStyle("H1", parent=styles["Normal"],
    fontSize=15, textColor=WHITE, fontName="Helvetica-Bold",
    spaceBefore=10, spaceAfter=6, leftIndent=0)

h2 = ParagraphStyle("H2", parent=styles["Normal"],
    fontSize=12, textColor=LBLUE, fontName="Helvetica-Bold",
    spaceBefore=8, spaceAfter=4, leftIndent=0)

body = ParagraphStyle("Body", parent=styles["Normal"],
    fontSize=10, textColor=colors.HexColor("#2c3e50"),
    fontName="Helvetica", leading=15, spaceAfter=4,
    alignment=TA_JUSTIFY)

bullet = ParagraphStyle("Bullet", parent=body,
    leftIndent=16, bulletIndent=6, spaceAfter=2,
    bulletFontName="Helvetica", bulletFontSize=10)

caption = ParagraphStyle("Caption", parent=styles["Normal"],
    fontSize=8.5, textColor=DGREY, fontName="Helvetica-Oblique",
    alignment=TA_CENTER, spaceAfter=6)

source_style = ParagraphStyle("Source", parent=styles["Normal"],
    fontSize=8, textColor=DGREY, fontName="Helvetica-Oblique",
    alignment=TA_LEFT)

# ── Helper builders ──────────────────────────────────────────────────────────
def section_header(text, story):
    """Teal banner with white text for section headings."""
    tbl = Table([[Paragraph(text, h1)]], colWidths=[W - 4*cm])
    tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), TEAL),
        ("ROWBACKGROUNDS", (0,0), (-1,-1), [TEAL]),
        ("LEFTPADDING",  (0,0), (-1,-1), 12),
        ("RIGHTPADDING", (0,0), (-1,-1), 12),
        ("TOPPADDING",   (0,0), (-1,-1), 7),
        ("BOTTOMPADDING",(0,0), (-1,-1), 7),
        ("ROUNDEDCORNERS", [4]),
    ]))
    story.append(Spacer(1, 6))
    story.append(tbl)
    story.append(Spacer(1, 4))

def info_box(text, story, bg=ACCENT):
    tbl = Table([[Paragraph(text, body)]], colWidths=[W - 4*cm])
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        ("TOPPADDING",   (0,0), (-1,-1), 7),
        ("BOTTOMPADDING",(0,0), (-1,-1), 7),
        ("BOX", (0,0), (-1,-1), 0.5, LBLUE),
    ]))
    story.append(tbl)
    story.append(Spacer(1, 6))

def make_table(headers, rows, story, col_widths=None):
    data = [[Paragraph(f"<b>{h}</b>", ParagraphStyle("th", parent=body,
                textColor=WHITE, fontName="Helvetica-Bold", fontSize=9.5)) for h in headers]]
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        data.append([Paragraph(str(c), body) for c in row])
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    t = Table(data, colWidths=cw, repeatRows=1)
    ts = TableStyle([
        ("BACKGROUND", (0,0), (-1,0), BLUE),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [WHITE, LGREY]),
        ("GRID", (0,0), (-1,-1), 0.4, colors.HexColor("#bdc3c7")),
        ("LEFTPADDING",  (0,0), (-1,-1), 8),
        ("RIGHTPADDING", (0,0), (-1,-1), 8),
        ("TOPPADDING",   (0,0), (-1,-1), 5),
        ("BOTTOMPADDING",(0,0), (-1,-1), 5),
        ("VALIGN", (0,0), (-1,-1), "TOP"),
    ])
    t.setStyle(ts)
    story.append(t)
    story.append(Spacer(1, 8))

def centered_image(path, story, width_cm=14, caption_text=""):
    img = RLImage(path, width=width_cm*cm, height=None)
    # Preserve aspect ratio
    from PIL import Image as PILImage
    with PILImage.open(path) as im:
        iw, ih = im.size
    h = (width_cm * cm) * ih / iw
    img = RLImage(path, width=width_cm*cm, height=h)
    tbl = Table([[img]], colWidths=[W - 4*cm])
    tbl.setStyle(TableStyle([
        ("ALIGN", (0,0), (-1,-1), "CENTER"),
        ("BACKGROUND", (0,0), (-1,-1), LGREY),
        ("BOX", (0,0), (-1,-1), 0.5, colors.HexColor("#bdc3c7")),
        ("TOPPADDING", (0,0), (-1,-1), 8),
        ("BOTTOMPADDING", (0,0), (-1,-1), 8),
    ]))
    story.append(tbl)
    if caption_text:
        story.append(Paragraph(caption_text, caption))
    story.append(Spacer(1, 8))

# ── Page template with header/footer ─────────────────────────────────────────
def on_page(canvas, doc):
    canvas.saveState()
    # Header bar
    canvas.setFillColor(BLUE)
    canvas.rect(0, H - 1.4*cm, W, 1.4*cm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica-Bold", 9)
    canvas.drawString(2*cm, H - 0.9*cm, "Synapse & Classification")
    canvas.setFont("Helvetica", 8)
    canvas.drawRightString(W - 2*cm, H - 0.9*cm, "Neuroscience | Medical Physiology")
    # Footer
    canvas.setFillColor(BLUE)
    canvas.rect(0, 0, W, 1.0*cm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica", 8)
    canvas.drawString(2*cm, 0.35*cm, "Sources: Guyton & Hall | Neuroscience: Exploring the Brain | Junqueira's Histology")
    canvas.drawRightString(W - 2*cm, 0.35*cm, f"Page {doc.page}")
    canvas.restoreState()

# ── Build story ───────────────────────────────────────────────────────────────
story = []

# ── Cover / Title block ───────────────────────────────────────────────────────
cover_data = [[
    Paragraph("SYNAPSE", title_style),
    Paragraph("&amp; its Classification", subtitle_style),
    Spacer(1, 6),
    Paragraph("Anatomical · Physiological · Functional · Chemical · Morphological", subtitle_style),
]]
cover_tbl = Table([[
    Paragraph("SYNAPSE &amp; ITS CLASSIFICATION", title_style),
]], colWidths=[W - 4*cm])
cover_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), BLUE),
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    ("TOPPADDING",   (0,0), (-1,-1), 18),
    ("BOTTOMPADDING",(0,0), (-1,-1), 6),
]))
story.append(cover_tbl)

sub_tbl = Table([[
    Paragraph("Anatomical &nbsp;·&nbsp; Physiological &nbsp;·&nbsp; Functional &nbsp;·&nbsp; Chemical &nbsp;·&nbsp; Morphological", subtitle_style),
]], colWidths=[W - 4*cm])
sub_tbl.setStyle(TableStyle([
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    ("LEFTPADDING",  (0,0), (-1,-1), 20),
    ("RIGHTPADDING", (0,0), (-1,-1), 20),
    ("TOPPADDING",   (0,0), (-1,-1), 8),
    ("BOTTOMPADDING",(0,0), (-1,-1), 10),
]))
story.append(sub_tbl)
story.append(Spacer(1, 12))

# ── Definition ────────────────────────────────────────────────────────────────
info_box(
    "<b>Definition:</b> A <b>synapse</b> is a specialized junction where a neuron contacts and "
    "transmits information to another neuron, muscle fiber, or gland cell. The term was coined "
    "by Charles Sherrington (1897), from the Greek meaning 'to clasp.' It consists of three "
    "components: the <b>presynaptic terminal</b>, the <b>synaptic cleft</b> (200-300 Å wide), "
    "and the <b>postsynaptic membrane</b>.",
    story
)

# ═══════════════════════════════════════════════════════════════════════════════
# 1. ANATOMICAL
# ═══════════════════════════════════════════════════════════════════════════════
section_header("1.  Anatomical Classification  (by site of contact)", story)
story.append(Paragraph(
    "Based on which part of the postsynaptic neuron the presynaptic axon terminal contacts.", body))
story.append(Spacer(1, 4))

centered_image(
    img_paths["anatomical"], story, width_cm=13.5,
    caption_text="Figure 1. Three morphological types of CNS synapses: Axosomatic, Axodendritic, and Axoaxonic.\n"
                 "(Source: Junqueira's Basic Histology, p. 428)"
)

make_table(
    ["Type", "Contact Site", "Key Features", "Function"],
    [
        ["<b>Axodendritic</b>", "Axon → Dendrite", "Most common; often on dendritic spines; linked to learning & memory", "Mainly excitatory"],
        ["<b>Axosomatic</b>", "Axon → Cell body (soma)", "Strong influence over firing threshold; near axon hillock", "Often inhibitory"],
        ["<b>Axoaxonic</b>", "Axon → Axon", "Modulates other synapses; causes presynaptic inhibition/facilitation", "Modulatory"],
        ["<b>Dendrodendritic</b>", "Dendrite → Dendrite", "Less common; found in olfactory bulb, retina", "Bidirectional signaling"],
    ],
    story,
    col_widths=[3.5*cm, 3.5*cm, 7*cm, 3.5*cm]
)

story.append(Paragraph(
    "<i>Note: On a typical anterior motor neuron, 80-95% of presynaptic terminals contact dendrites "
    "and only 5-20% contact the soma. Up to 10,000-200,000 synaptic knobs may be present on a single neuron.</i>",
    source_style))
story.append(Spacer(1, 8))

# ═══════════════════════════════════════════════════════════════════════════════
# 2. PHYSIOLOGICAL
# ═══════════════════════════════════════════════════════════════════════════════
section_header("2.  Physiological Classification  (by effect on postsynaptic cell)", story)

make_table(
    ["Feature", "Excitatory Synapse", "Inhibitory Synapse"],
    [
        ["Neurotransmitter", "Glutamate, Acetylcholine", "GABA, Glycine"],
        ["Effect on membrane", "Depolarization", "Hyperpolarization"],
        ["Postsynaptic potential", "EPSP (Excitatory PSP)", "IPSP (Inhibitory PSP)"],
        ["Ion permeability", "Increases Na⁺ (and other cations)", "Increases K⁺ or Cl⁻"],
        ["Membrane potential shift", "Toward threshold (fires AP)", "Away from threshold (inhibits AP)"],
        ["Location", "Often axodendritic", "Often axosomatic / axoaxonic"],
    ],
    story,
    col_widths=[5*cm, 6.5*cm, 6*cm]
)

info_box(
    "<b>Synaptic Summation:</b> The postsynaptic neuron integrates hundreds to thousands of EPSPs "
    "and IPSPs simultaneously. <b>Temporal summation</b> occurs when rapid repeated impulses from "
    "one synapse accumulate. <b>Spatial summation</b> occurs when multiple synapses fire at once. "
    "The final response is the algebraic sum of all inputs.",
    story
)

# ═══════════════════════════════════════════════════════════════════════════════
# 3. FUNCTIONAL
# ═══════════════════════════════════════════════════════════════════════════════
section_header("3.  Functional Classification  (Electrical vs. Chemical)", story)

centered_image(
    img_paths["elec_chem"], story, width_cm=14,
    caption_text="Figure 2. (A) Electrical synapse via gap junctions (connexons). (B) Chemical synapse "
                 "showing synaptic vesicles, neurotransmitter release, and postsynaptic receptors.\n"
                 "(Source: Neuroscience: Exploring the Brain, 5th Ed., p. 392)"
)

make_table(
    ["Feature", "Electrical Synapse", "Chemical Synapse"],
    [
        ["Structure", "Gap junctions (connexons / connexins)", "Synaptic vesicles, cleft, receptors"],
        ["Cleft gap", "~3 nm", "200-300 Å (20-30 nm)"],
        ["Signal mediator", "Ionic current (direct)", "Neurotransmitter (indirect)"],
        ["Direction", "Mostly bidirectional", "Strictly unidirectional"],
        ["Speed", "Very fast (no delay)", "~0.5 ms synaptic delay"],
        ["Amplification", "No (signal may decrease)", "Yes (small signal → large response)"],
        ["Reliability", "Near fail-safe (large junctions)", "Variable; modifiable"],
        ["Plasticity", "Limited", "High (basis of learning)"],
        ["Examples", "Inferior olive, hypothalamic neurons, cardiac muscle", "Vast majority of CNS/PNS synapses"],
        ["Function", "Synchronizes neuronal populations", "Precise signal processing & modulation"],
    ],
    story,
    col_widths=[4*cm, 6*cm, 7.5*cm]  # adjusted
)

story.append(Paragraph(
    "<i>Electrical and chemical synapses can coexist and interact in the CNS. "
    "Electrical synapses are especially important where synchronized firing of groups of neurons is needed. "
    "– Guyton &amp; Hall, p. 568</i>",
    source_style))
story.append(Spacer(1, 8))

# ═══════════════════════════════════════════════════════════════════════════════
# 4. CHEMICAL
# ═══════════════════════════════════════════════════════════════════════════════
section_header("4.  Chemical Classification  (by neurotransmitter)", story)

story.append(Paragraph(
    "Synapses are named by the neurotransmitter released from the presynaptic terminal:", body))
story.append(Spacer(1, 4))

make_table(
    ["Synapse Type", "Neurotransmitter", "Receptor Types", "Location / Role"],
    [
        ["Cholinergic",    "Acetylcholine (ACh)",    "Nicotinic, Muscarinic",       "NMJ, autonomic ganglia, CNS cortex"],
        ["Glutamatergic",  "Glutamate",               "AMPA, NMDA, Kainate, mGluR",  "Most excitatory CNS synapses"],
        ["GABAergic",      "GABA",                    "GABA-A (ionotropic), GABA-B", "Most inhibitory CNS synapses"],
        ["Glycinergic",    "Glycine",                 "Glycine receptor (GlyR)",     "Spinal cord & brainstem inhibition"],
        ["Dopaminergic",   "Dopamine",                "D1-D5 receptors",             "Substantia nigra, mesolimbic pathway"],
        ["Serotonergic",   "Serotonin (5-HT)",        "5-HT1 – 5-HT7",              "Raphe nuclei; mood, sleep, appetite"],
        ["Noradrenergic",  "Norepinephrine",           "α1, α2, β1, β2",             "Locus coeruleus; arousal, stress"],
        ["Peptidergic",    "Substance P, Endorphins,\nNeuropeptide Y", "GPCRs",      "Pain modulation; widespread CNS"],
        ["Purinergic",     "ATP / Adenosine",          "P1 (adenosine), P2 (ATP)",   "CNS neuromodulation, autonomic"],
    ],
    story,
    col_widths=[3.5*cm, 3.5*cm, 5*cm, 5.5*cm]
)

info_box(
    "<b>Key principle:</b> Different receptor subtypes and second-messenger systems exist for the same "
    "transmitter, greatly multiplying possible effects. After release, transmitters are rapidly removed "
    "by enzymatic breakdown (e.g., AChE), glial reuptake, or endocytic recycling at presynaptic "
    "membrane receptors. – Junqueira's Basic Histology, p. 429",
    story
)

# ═══════════════════════════════════════════════════════════════════════════════
# 5. MORPHOLOGICAL
# ═══════════════════════════════════════════════════════════════════════════════
section_header("5.  Morphological Classification  (Gray's Types I &amp; II)", story)

story.append(Paragraph(
    "Based on <b>electron microscopy</b>, E.G. Gray (1959) classified synapses by the density of "
    "pre- and postsynaptic specializations and the shape of synaptic vesicles:", body))
story.append(Spacer(1, 4))

make_table(
    ["Feature", "Gray Type I (Asymmetric)", "Gray Type II (Symmetric)"],
    [
        ["Postsynaptic density",   "Prominent (thick)",              "Equal / thin on both sides"],
        ["Synaptic vesicle shape", "Round / spherical",              "Flattened / pleomorphic"],
        ["Synaptic cleft width",   "~30 nm (wider)",                 "~20 nm (narrower)"],
        ["Location",               "Dendritic spines & shafts (axodendritic)", "Cell bodies & axon hillock (axosomatic, axoaxonic)"],
        ["Physiological effect",   "Excitatory (EPSP)",              "Inhibitory (IPSP)"],
        ["Main neurotransmitter",  "Glutamate",                      "GABA, Glycine"],
    ],
    story,
    col_widths=[4.5*cm, 6.5*cm, 6.5*cm]
)

story.append(Paragraph(
    "<i>Note: Synaptic structure cannot be resolved by routine H&amp;E staining. Silver precipitation "
    "methods (e.g., Golgi method) reveal synapses as oval bodies (boutons terminaux) on the "
    "postsynaptic cell surface. Axons may also form boutons en passant — multiple contacts along "
    "the axon before ending as a terminal bulb. – Histology: A Text and Atlas, p. 931</i>",
    source_style))
story.append(Spacer(1, 10))

# ═══════════════════════════════════════════════════════════════════════════════
# Summary Table
# ═══════════════════════════════════════════════════════════════════════════════
section_header("Summary Table", story)

make_table(
    ["Classification", "Subtypes"],
    [
        ["<b>Anatomical</b>",     "Axodendritic · Axosomatic · Axoaxonic · Dendrodendritic"],
        ["<b>Physiological</b>",  "Excitatory (EPSP) · Inhibitory (IPSP)"],
        ["<b>Functional</b>",     "Electrical (gap junctions) · Chemical (neurotransmitter-mediated)"],
        ["<b>Chemical</b>",       "Cholinergic · Glutamatergic · GABAergic · Glycinergic · Dopaminergic · Serotonergic · Noradrenergic · Peptidergic · Purinergic"],
        ["<b>Morphological</b>",  "Gray Type I (asymmetric, excitatory) · Gray Type II (symmetric, inhibitory)"],
    ],
    story,
    col_widths=[4.5*cm, 13*cm]
)

# References
story.append(HRFlowable(width="100%", thickness=0.5, color=LBLUE))
story.append(Spacer(1, 4))
story.append(Paragraph("<b>Key References</b>", h2))
refs = [
    "Guyton AC, Hall JE. Textbook of Medical Physiology, 14th Ed. pp. 568-570.",
    "Bear MF, Connors BW, Paradiso MA. Neuroscience: Exploring the Brain, 5th Ed. pp. 391-396.",
    "Eroschenko VP. Histology: A Text and Atlas with Correlated Cell and Molecular Biology. pp. 929-931.",
    "Mescher AL. Junqueira's Basic Histology: Text and Atlas, 17th Ed. pp. 427-429.",
    "Gray EG. Axo-somatic and axo-dendritic synapses of the cerebral cortex. J Anat. 1959;93:420-433.",
]
for r in refs:
    story.append(Paragraph(f"• {r}", source_style))
story.append(Spacer(1, 6))

# ── Render ─────────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=2*cm, rightMargin=2*cm,
    topMargin=2*cm, bottomMargin=1.5*cm,
    title="Synapse and Its Classification",
    author="Orris Medical"
)
doc.build(story, onFirstPage=on_page, onLaterPages=on_page)
print(f"PDF saved to {OUTPUT}")